Podcasts about Kras

"It's critical to identify those mutations found that are driving the cancer's growth and guide the personalized treatment based on those results. And important to remember, too, early testing is crucial for patients with non-small cell lung cancer (NSCLC). In studies, it has been found to be associated with improved survival outcomes and reduced mortality," ONS member Vicki Doctor, MS, BSN, BSW, RN, OCN®, precision medicine director at the City of Hope Atlanta, GA, Chicago, IL, and Phoenix, AZ, locations, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the oncology nurse's role in NSCLC biomarker testing. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  This podcast is sponsored by Lilly Oncology and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. Episode Notes  This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 363: Lung Cancer Treatment Considerations for Nurses Episode 359: Lung Cancer Screening, Early Detection, and Disparities Episode 238: Cancer Genomics for Every Oncology Nurse Episode 157: Biomarker Testing Improves Outcomes for Patients With Non-Small Cell Lung Cancer ONS Voice articles: Non-Small Cell Lung Cancer Prevention, Screening, Diagnosis, Treatment, Side Effects, and Survivorship Only a Third of Patients With Advanced Cancer Get Biomarker Testing, Limiting Use of Potentially Effective Precision Therapies Precision Medicine in Lung Cancer: How Comprehensive Testing Optimizes Patient Outcomes Targeted Therapies Are Transforming the Treatment of Non-Small Cell Lung Cancer ONS book: Guide to Cancer Immunotherapy (second edition) ONS course: Genomic Foundations for Precision Oncology Clinical Journal of Oncology Nursing article: Using Nurse Navigators to Improve Timeliness of Biomarker Testing for Non-Small Cell Lung Cancer Oncology Nursing Forum article: Precision Medicine Testing and Disparities in Health Care for Individuals With Non-Small Cell Lung Cancer: A Narrative Review Other ONS resources: Best Practices for Biomarker Testing in Non-Small Cell Lung Cancer: A Case Study Genomics and Precision Oncology Learning Library Genomics Case Study: Precision Medicine in the Setting of Metastatic Non-Small Cell Lung Cancer Biomarker Database (refine by non-small cell lung cancer) Genomic Biomarkers Huddle Card Targeted Therapy Huddle Card National Comprehensive Cancer Network homepage To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org Highlights From This Episode "These biomarkers are used to provide information about cancer's characteristics or behavior. In oncology precision medicine specifically, molecular tests can help with diagnosing a cancer that is maybe an unknown primary. It can help with monitoring response to therapy, detect recurrence of disease before other tests can find that, predict prognosis or how aggressive the cancer may be, and guide treatment decisions for targeted therapies." TS 3:14 "Some of the key biomarkers recommended by the National Comprehensive Cancer Network (NCCN) to be tested in patients who have NSCLC are EGFR, ALK, KRAS, BRAF, MET exon 14 skipping mutation, HER2 which is a protein expression from an ErbB protein, PD-L1 which is a protein expression that's used to guide immunotherapy choices, and then finally there are three fusions: ROS1, RET, and NTRK. [These] are pretty rare but really important to be tested for in patients who have NSCLC." TS 3:46 "Another important challenge for nurses related to this topic is that these results may not reveal a targeted mutation for the patient and that could be very disappointing. So, being able to provide that emotional support to a patient if they have that result … you can actually reinforce with them that if [they] go onto another treatment that the physician decides to put [them] on, the tumor can change. New pathogenic variants can develop based on the treatment that they're getting, and another test can be done. And maybe at that time—a new biomarker that could be targeted—we'd be seeing on the new test." TS 7:32  "Another circumstance we didn't talk about yet is that maybe the result came back saying that the quality was not sufficient. And sometimes that happens, but that doesn't mean that we're at the end of the road, necessarily. So, you could explain to the patient that that may mean that possibly, a new biopsy would be ordered by the physician. Or if a new biopsy or another tissue sample is not available, then maybe the physician would pivot to sending a blood specimen for the molecular testing. So that would definitely be a way [nurses] could support their patients." TS 11:52 "In the case of patients with NSCLC, early testing is so important. So, advocating for that prompt biomarker testing to be done, making sure that it's comprehensive, that it's actually looking for all of those—I think it was 12 biomarkers—that I mentioned earlier. That this testing is done as soon as possible after diagnosis or progression. Something that I talk about all the time—personalized care, precision medicine—really matters. So, tailoring treatments for patients based on the biology of the tumor that's driving the cancer's growth is really crucial if you're going to be working as an oncology nurse. Another crucial thing, because it's changing so quickly, is to stay informed." TS 16:23

Under fredagens jubileumssändning hoppas vi att allt flyter på men inget kalas utan kras! Eller? Lyssna på alla avsnitt i Sveriges Radio Play. Ett nyfiket och underhållande aktualitetsprogram med lyssnaren i fokus.Anders berättar om den gången han anordnade en bröllopsfest för 250 personer och den översta delen av tårtan gled ner på golvet. Och Jenny minns tillbaka till när hon under en hemmafest skulle skoja med hennes kille men det slutade med ett krossat akvarium!I extramaterialet ringer vi upp våra kära före detta medarbetare – Oscar och Björnpojken!

In this episode, Dr Rachel Grisham and Dr Kathleen Moore discuss newly approved treatments for low-grade serous ovarian cancer (LGSOC) and how recent research has transformed the therapeutic landscape for these patients, including:Molecular distinctions between low-grade and high-grade serous ovarian cancer that can guide therapy selectionThe recently approved targeted therapy combination regimen of avutometinib and defactinib for KRAS-mutant LGSOC (RAMP 201)Promising future directions for patients with LGSOC based on ongoing studies such as RAMP 301 and CHAMELEON Presenters:Rachel Grisham, MDSection Head of Ovarian CancerMemorial Sloan Kettering Cancer CenterDirector Gynecologic Medical Oncology, MSKCC WestchesterNew York, New YorkKathleen N. Moore, MD, MS, FASCODeputy Director and Cancer Therapeutics Co-LeadStephenson Cancer Center at the University of OklahomaProfessorDepartment of OB/GynASCO BODOklahoma City, Oklahoma Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

In this episode of JCO PO Article Insights, host Dr. Jiasen He summarizes the article, "Somatic Mutation Profiles of Colorectal Cancer by Birth Cohort" by Gilad, et al published October 11, 2025. TRANSCRIPT Jiasen He: Hello, and welcome to the JCO Precision Oncology Article Insights. I am your host, Jiasen He, and today, we will be discussing the JCO Precision Oncology article, "Somatic Mutation Profiles of Colorectal Cancer by Birth Cohort," by Dr. Gilad and colleagues. Early-onset colorectal cancer is defined as colorectal cancer diagnosed before the age of 50. Several reports have suggested that early-onset colorectal cancer has unique characteristics. Compared with late-onset colorectal cancer, early-onset colorectal cancer cases are more commonly found in the distal colon or rectum, tend to be diagnosed at more advanced stages, and may display unfavorable histologic features. Although the overall incidence of colorectal cancer has declined in recent decades, the incidence of early-onset colorectal cancer continues to rise. This increase appears to be driven by birth cohort effects. The reasons behind this rise remain unclear but are likely multifactorial, involving changes in demographics, diet, lifestyle, environmental exposures, and genetic predisposition. At the same time, studies have shown conflicting results regarding whether there are differences in the mutation profiles between early-onset and late-onset colorectal cancer. Therefore, it is crucial to explore whether colorectal cancer somatic mutational landscape differs across birth cohorts, as this could provide important insight into generational shifts in colorectal cancer incidence. To address this question, the authors conducted a retrospective study to characterize the mutation spectrum of colorectal cancer across different birth cohorts. Consecutive colorectal cancer patients who underwent somatic next-generation sequencing at the University of Chicago pathology laboratory between 2015 and 2022 were retrospectively identified. Tumors were tested for 154 to 168 genes and categorized as either microsatellite stable or high according to established thresholds. Patients with hereditary cancer syndromes or inflammatory bowel disease were excluded. Participants were then grouped into birth cohorts by decades, as well as into two major groups: those born before 1960 and after 1960. Genes that were identified in at least 5% of the sample were selected and grouped into 10 canonical cancer signaling pathways. These genes and pathways were then included in the analysis to explore their association with colorectal cancer across different birth cohorts and age groups. A total of 369 patients were included in the study, with a median birth year of 1955 and a median age at colorectal cancer diagnosis of 62.9 years. 5.4% were identified as having microsatellite-high tumors. The median tumor mutational burden was 5 mutations per megabase for microsatellite-stable tumors and 57.7 mutations per megabase for microsatellite-high tumors. Patients with microsatellite-high tumors tended to have earlier birth years and were diagnosed at an older age. However, after adjusting for potential confounders, neither birth year nor age remained statistically significant. Similarly, after controlling for confounders, no significant associations were observed between birth year or age and mutation burden. In this cohort, APC, TP53, and KRAS were the most frequently mutated genes. No statistically significant differences in the prevalence of gene mutations were observed across birth cohorts. Correspondingly, the most affected signaling pathways were the Wnt, TP53, and (RTK)/RAS pathways. Similar to the gene-level finding, no significant differences in the prevalence of these pathways were identified among birth cohorts. When examining patients born before and after 1960, the authors found that the older birth cohorts were diagnosed at an older age and had higher tumor mutational burden. However, no significant differences were observed in any of the genes or pathways analyzed. Among microsatellite-stable tumors, 18.3% were classified as early-onset colorectal cancer, while 81.1% were late-onset colorectal cancer. Consistent with previous reports, early-onset colorectal cancers in this cohort were more likely to be left-sided and more common among more recent birth cohorts. However, no significant differences were identified in any of the examined genes or pathways when comparing early-onset to late-onset colorectal cancer. In this cohort, a higher prevalence of early-onset colorectal cancer was observed among more recent birth cohorts, consistent with previous reports. Still, no distinct mutational signature was identified between the early and late birth cohorts. The authors proposed that the lack of distinct mutational profile by age or birth cohort may be due to the limited number of key molecular pathways driving colorectal cancer. Although environmental exposures likely differ across generations, the downstream effects may have converged on similar biological mechanisms, leading to comparable somatic mutations across cohorts. Alternately, they proposed that the observed birth cohort differences in colorectal incidence may be driven by distinct mutation signatures, epigenetic alterations, or changes in the immune microenvironment rather than variations in canonical gene mutations. As the authors noted, given the retrospective nature of this study, its modest sample size, and the predominance of advanced-stage tumors, larger prospective studies are needed to validate these findings. In summary, this study found no significant differences in the mutational landscape of colorectal cancer across birth cohorts or age groups. The authors proposed that the generational shift in colorectal cancer incidence is unlikely to be driven by changes in the underlying tumor genomics. However, larger prospective studies are needed to validate these findings. Thank you for tuning in to JCO Precision Oncology Article Insights. Do not forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

On this week's episode, Josh and Michael exchange the established treatment landscape of EGFR and ALK mutant NSCLC for the developing management of disease harbouring KRAS and MET mutations. The most common mutation meets one of the least common in this battle of therapeutic tenacity.Studies discussed in this episode:INSIGHT-2KRYSTAL-12For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

About This Episode: This week on Stageworthy, host Phil Rickaby is joined by Michael Kras, playwright, director, and one of Canada's busiest magic designers. Michael has designed magic and illusions for theatres across the country and is the resident magic and illusions lead for the North American tour of Harry Potter and the Cursed Child. He also joins the Tarragon Theatre's Greenhouse Residency to develop his new solo play Love Me Back, a piece that blends sleight-of-hand magic with storytelling. This episode explores: Michael's path from magician to playwright and director Integrating magic into theatre in meaningful ways The role of magic design in Harry Potter and the Cursed Child The Hamilton theatre scene and its challenges Writing for young audiences and why those stories matter The creation of his magic book Synthesis and Secrets Developing his new play Love Me Back at Tarragon's Greenhouse Residency Guest:

V naši družbi je bil znani pisec planinskih vodnikov Gorazd Gorišek, ki je prehodil že mnogo planinskih in gorskih kotičkov naše dežele. Med drugim nas bo popeljal na Kras in po Primorski, saj je nedavno uredil vodnik, v katerem je zbranih kar 45 izletov. Pridružite se nam na jesenskem potepu med ruj, ki vabi s svojimi ognjenimi barvami!

V naši družbi je bil znani pisec planinskih vodnikov Gorazd Gorišek, ki je prehodil že mnogo planinskih in gorskih kotičkov naše dežele. Med drugim nas bo popeljal na Kras in po Primorski, saj je nedavno uredil vodnik, v katerem je zbranih kar 45 izletov. Pridružite se nam na jesenskem potepu med ruj, ki vabi s svojimi ognjenimi barvami!

Ime tedna je postal Nick Vovk, diplomirani filozof, kulturni antropolog, etnolog, magister razvojnih študij na Univerzi v Cambridgeu in predvsem humanitarec. Kot sodelavec nevladne organizacije Danski svet za begunce je specializiran za področje eksplozivnih ubojnih sredstev. Že večkrat je v Gazi pomagal žrtvam eksplozivnih orožij in pri razdeljevanju najnujnejše pomoči. Pred tem je deloval tudi na drugih kriznih žariščih, predvsem na Kosovu in v Ukrajini. Foto: Arhiv Nicka Vovka Kandidatki sta bili še: Maja Žugič, odgovorna urednica Cicibana, najstarejše slovenske otroške revije, ki letos praznuje 80 let. Maja Žugič je tudi pobudnica akcije, v okviru katere so danes vsi prvošolci, tudi v zamejstvu, brezplačno prejeli svoj izvod tematske številke Ciciban gre v šolo. Od prve številke leta 1945 je doslej izšlo že več kot 900 številk revije, ki velja za enega ključnih stebrov mladinske in otroške književnosti. Vesna Guštin, kulturna delavka, pisateljica, predsednica Kulturnega društva Kraški dom in duša Kraške ohceti, ki aktivno sodeluje pri pripravi ter ohranjanju tega največjega etnografskega praznika na Tržaškem Krasu. Je tudi avtorica knjige Živio kraška ohcet!, v kateri je leta 2018 popisala in ovrednotila pol stoletja Kraške ohceti. To tradicijo je leta 1968 ponovno oživela zadruga Naš Kras, odtlej jo prirejajo vsaki dve leti; ta konec tedna so poročili 28. par.  

Send us a textOur guest today is the author of ‘Radical Product Thinking: The New Mindset for Innovating Smarter', a book whose methodology is now being used in over 40 countries and has also been translated into Chinese and Japanese. She is an entrepreneur, speaker, consultant and product leader who has participated in five acquisitions, two of which were companies that she founded. Meet the one and only, the radical Radhika Dutt!    An MIT graduate, Radhika works with organizations ranging from high-tech startups to multinationals on building radical products that create a fundamental change. Radhika has built products in a wide range of industries including broadcast, media and entertainment, telecom, advertising technology, government, consumer apps, robotics, and even wine. She is currently Advisor on Product Thinking to the Monetary Authority of Singapore (Singapore's central bank and financial regulator). Radhika is working on her second book, ‘Escaping the Performance Trap: Why Goals and Targets Backfire and What Actually Works'.[2:57s] Radhika's genesis story[10:14s] Radical Product Thinking – breaking it down[16:56s] Applying Radical Product Thinking in today's VUCA world[23:45s] How can KPIs, OKRs and KRAs evolve with Radical Product Thinking[30:36s] The methodology of Objectives Hypotheses & Learnings – OHLs [45:56s] Radhika's vision for the near future and her upcoming book ‘Escaping the Performance Trap'RWL: Read Radhika's book ‘Radical Product Thinking' Find out more about her work at https://rdutt.com/Connect with Radhika on LinkedInConnect with Vinay on X (formerly Twitter) and LinkedIn What did you think about this episode? What would you like to hear more about? Or simply, write in and say hello! podcast@c2cod.comSubscribe to us on your favorite platforms – Google Podcasts, Apple Podcasts, Spotify, Overcast, Tune In Alexa, Amazon Music, Pandora, Jio Saavn and more. This podcast is sponsored by C2C-OD, your Organizational Development consulting partner ‘Bringing People and Strategy Together'. Follow @c2cod on Twitter, LinkedIn, Instagram, Facebook 

Vidcast:  https://www.instagram.com/p/DN0-HNvXPcP/An already FDA-approved cancer vaccine was spectacularly effective in controlling pancreatic cancers that carry the KRAS markers.  A multi-center phase 1 study, helmed by oncologists at New York's Sloan Kettering and Texas' MD Anderson, studied the vaccine labeled ELI-002 developed by Boston's Elicio Therapeutics.  The results demonstrated that the vaccine can trigger a vigorous killer T cell response to this KRAS marker carried by 88% of pancreatic cancers. They also showed that 65% of patients who mounted this T cell response to the vaccine enjoyed no radiographic progression of their cancers.  Even more exciting, five of the sewpatients were free of tumor relapse without any subsequent therapy following the vaccine.  When the study ended after nearly 20 months, these excellent responders were all alive without evidence of cancer recurrence.  In contrast, the untreated controls developed cancer relapses in an average of 3 months and only survived an average of 15 months.Unlike most cancer vaccines that are custom produced for each patient's tumor, ELI-002 can be mass produced making it readily available for administration and less expensive.  A phase 2 trial of the vaccine is already in progress.Pancreatic cancer is one of the deadliest cancers, with only about 13% of patients surviving five years after diagnosis and recurrence rates as high as 80% within two years of surgery. Hopefully, this vaccine immunotherapy will help change those dismal statistics.https://www.nature.com/articles/s41591-025-03876-4#cancer #pancreatic #vaccine #ELI002 #elicio #iommunotherapy

Bratislava 24. augusta (TASR) – Pre pacientov s ochorením oka zvaným keratokonus je problém nastaviť okuliare. Častokrát ani s nimi takmer nevidia. Okrem chirurgického zákroku vedia na zlepšenie zraku pomôcť tvrdé kontaktné šošovky. V relácii TASR TV Zdravie to konštatoval optometrista Michal Krasňanský. . „Keratokonus je ochorenie, pri ktorom rohovka stráca svoj pravidelný tvar a začína vyklenovať, čo vážne ovplyvňuje naše videnie,“ vysvetlil. Ako dodal, pred špeciálnym vyšetrením býva často zamieňané s astigmatizmom.

In this episode, Dr. Paul Wheatley-Price chats with Dr. Adrian Sacher on everything there is to know about KRAS lung cancer. What is KRAS lung cancer, how is it tested, and what it means in terms of treatment options for those who have this subtype of lung cancer. Dr. Adrian Sacher is a Thoracic Medical Oncologist at the Princess Margaret Cancer Centre and Assistant Professor in the Departments of Medicine & Immunology at the University of Toronto.

Dr Bill Nelson and Dr Michael Pishvaian discuss the targeting of KRAS mutations in pancreatic cancer to develop new treatment options for a disease that has been historically difficult to care for.

Dr Bill Nelson and Dr Nilo Azad discuss the decades-long research effort to develop treatments targeting KRAS mutations and the importance of federal funding in bringing those treatments to patients. 

Kras nudi polnost doživetij na področju dediščine, tudi za rekreativce in navdušene kulinarike. Ob razvoju trajnostnega turizma želijo delovati tudi na razvoju lokalnega kmetijstva ter podjetništva. V Štanjelu so odprli tudi prvi Muzej slovenskega jezika in knjige. Pogovarjali smo se z županom Komna Erikom Modicem.

Kras nudi polnost doživetij na področju dediščine, tudi za rekreativce in navdušene kulinarike. Ob razvoju trajnostnega turizma želijo delovati tudi na razvoju lokalnega kmetijstva ter podjetništva. V Štanjelu so odprli tudi prvi Muzej slovenskega jezika in knjige. Pogovarjali smo se z županom Komna Erikom Modicem.

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

Pred tremi leti se je več kot tisoč 500 poklicnih in prostovoljnih gasilcev spopadalo z največjim požarom v zgodovini samostojne Slovenije. Goreči Kras je zaposloval še veliko drugih služb iz sistema zaščite in reševanja, na delu so bili prostovoljci, gozdarska stroka je še danes vpeta v sanacijo. Tri leta pozneje nas na kraški požar opomnita pogled na pokrajino ter spraševanje, kaj bo drugače, če se ponovi. O novostih in pridobitvah, ki so posledica kraškega požara, v tokratnem Studiu ob 17-ih. Gostje: Leon Behin, generalni direktor Uprave za zaščito in reševanje; Mitja Vidmar, vodja Sektorja za izvajanje podpore gašenju iz zraka; Simon Vendramin, poveljnik Gasilske enote Nova Gorica; Matej Kravanja, območna enota Zavoda za gozdove Sežana; Boris Budal. namestnik direktorja Zavoda za gasilno in reševalno službo Sežana. Avtorica oddaje Tjaša Škamperle

On this episode of Translating Proteomics, Parag, Andreas, and special guest Don Kirkpatrick answer questions submitted by the Translating Proteomics community. They cover:Needs in plasma proteomicsHow proteomics impacts drug development – with special guest Don Kirkpatrick Ph.D.!How lifestyle impacts the proteomeHow the Nautilus Proteome Analysis Platform is impacting tau and Alzheimer's disease researchReferencesShome et al., 2022 - Serum autoantibodyome reveals that healthy individuals share common autoantibodieshttps://www.sciencedirect.com/science/article/pii/S2211124722006489LaBaer Lab paper investigating autoantibody levels in plasma and their relationship to health.Sylman et al., 2018 - A Temporal Examination of Platelet Counts as a Predictor of Prognosis in Lung, Prostate, and Colon Cancer Patientshttps://www.nature.com/articles/s41598-018-25019-1Mallick lab paper investigating temporal changes in platelets and their associations with cancer biology.Krönke et al., 2014 - Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cellshttps://www.science.org/doi/10.1126/science.1244851Seminal paper describing selective protein degradation caused by lenalidomide.Fink and Ebert 2015 - The novel mechanism of lenalidomide activityhttps://ashpublications.org/blood/article/126/21/2366/34644/The-novel-mechanism-of-lenalidomide-activityReview of research elucidating the mechanisms of lenalidomide activityNdoja et al., 2025 - COP1 Deficiency in BRAFV600E Melanomas Confers Resistance to Inhibitors of the MAPK Pathwayhttps://www.mdpi.com/2073-4409/14/13/975Describe links between kinase inhibitor vemurafenib and changes in ETV transcription factor degradationSong et al., 2022 - RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacyhttps://aacrjournals.org/cancerdiscovery/article/12/1/204/675622/RTK-Dependent-Inducible-Degradation-of-Mutant-PI3KUse proteomics to discover that inavolisib acts through selective degradation of mutant PI3KαCanon et al., 2019 - The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunityhttps://www.nature.com/articles/s41586-019-1694-1Covers the development of an inhibitor of KRAS mutant KRAS (G12C).Schneider et al., 2024 - Feeding gut microbes to nourish the brain: unravelling the diet-microbiota-gut-brain axishttps://www.nature.com/articles/s42255-024-01108-6Review on the gut-brain axisWebpage for Johanna Lampe's Lab at Fred Hutch Cancer Center

BUFFALO, NY – June 27, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights.” In this study, researchers led by first authors Cleto Dantas Nogueira from the Federal University of Ceará and Argos Pathology Laboratory and Samuel Frota from Argos Pathology Laboratory, along with corresponding author Fabio Tavora from the previously mentioned institutions and Messejana Heart and Lung Hospital, investigated how HER2 gene mutations appear in cases of non-small cell lung cancer (NSCLC) in Northeastern Brazil. The team found that HER2 mutations showed significant genetic diversity and were often associated with other cancer-related genetic changes. These findings revealed diagnostic and treatment challenges in a population that is rarely studied, emphasizing the need for expanded access to molecular testing and targeted therapies. HER2 mutations are a known factor in several cancers, including breast and gastric cancers. In lung cancer—particularly NSCLC—these mutations are less common but remain clinically significant. Most existing research on HER2-mutated lung cancer focuses on high-income countries, leaving important gaps in knowledge about underrepresented regions such as Latin America. This study helps fill that gap by analyzing 13 patients with HER2-mutated NSCLC using clinical, pathological, and genomic data. The patients ranged in age from 34 to 82 years, and more than half were women. About half had never smoked. Their tumors often displayed complex genetic profiles, including additional mutations in genes such as TP53, KRAS, and STK11. The most common HER2 mutation identified was an insertion in exon 20, a known hotspot for activating mutations. “Trastuzumab deruxtecan (T-DXd) is the first HER2-targeted agent to show clinical efficacy in HER2-mutant non-small cell lung cancer (HER2m NSCLC).” Treatment strategies among the patients varied. Only one individual received HER2-targeted therapy. Most were treated with surgery, chemotherapy, immunotherapy, or a combination of these approaches. Outcomes also differed, with some patients surviving for years and others dying within months of diagnosis. These findings reinforce the need for early diagnosis and improved access to advanced treatments, particularly in low-resource settings. The study emphasizes the value of comprehensive molecular profiling in NSCLC. Because HER2 mutations often occur alongside other genetic alterations, full genomic analysis is crucial for guiding treatment decisions. Yet, such testing is not always available. The researchers propose a tiered diagnostic approach, beginning with basic screening and expanding to more advanced tests when necessary, to enhance patient care. This study provides valuable insights into the molecular characteristics of HER2-mutated NSCLC in a Brazilian population, highlighting the complexity and clinical relevance of these alterations. Larger studies are needed to clarify the prevalence and prognostic significance of HER2 mutations, as well as their impact on treatment response and survival. This knowledge is essential for advancing effective HER2-targeted therapies. The findings also support broader implementation of international clinical guidelines in Latin America and highlight the critical need to include underrepresented populations in cancer research. DOI - https://doi.org/10.18632/oncotarget.28737 Correspondence to - Fabio Tavora - stellacpak@outlook.com Video short - https://www.youtube.com/watch?v=hr5R9iDBFFI To learn more about Oncotarget, please visit https://www.oncotarget.com. MEDIA@IMPACTJOURNALS.COM

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 

JCO PO author Dr. Philip Philip at Henry Ford Cancer Institute and Wayne State University shares insights into his JCO PO article, “Incorporating Circulating Tumor DNA Testing Into Clinical Trials: A Position Paper by the National Cancer Institute GI Oncology Circulating Tumor DNA Working Group.” Host Dr. Rafeh Naqash and Dr. Philip discuss how prospective trials are required to clarify the role of ctDNA as a valid surrogate end point for progression-free or overall survival in GI cancers. Transcript Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, we are excited to be joined by Dr. Philip Philip, Chair of Hematology and Oncology, as well as leader of GI and Neuroendocrine Oncology. He's also the Professor of Oncology and Pharmacology, as well as Co-Leader of the Pancreatic Cancer Program and Medical Director of the Cancer Clinical Trial and Translational Research Office at the Henry Ford Cancer Institute at Wayne State University. Dr. Philip is also the Senior Corresponding Author of the JCO Precision Oncology article entitled, "Incorporating Circulating Tumor DNA Testing into Clinical Trials: A Position Paper by the National Cancer Institute GI Oncology Circulating Tumor DNA Working Group." At the time of this recording, our guest's disclosures will be linked in the transcript. Dr. Philip, welcome to our podcast, and thank you so much for joining us today. Dr. Philip Philip: Thank you so much, Dr. Naqash, for providing me this opportunity to be discussing this with you. Dr. Rafeh Naqash: This is a very timely and interesting topic. We've done a couple of podcasts on ctDNA before, but none that is an opinion piece or a guidance piece based on what you guys have done. Could you tell us what led to this perspective piece or guidance manuscript being published? There is some background to this. Could you tell us, for the sake of our listeners, what was the initial thought process of why you all wanted to do this? Dr. Philip Philip: The major reason for this was the fact that investigators were considering using ctDNA as a primary endpoint in clinical trials. Obviously, you hear my focus will be on gastrointestinal cancers. So, the idea was, can we use ctDNA instead of using the traditional endpoints such as disease-free survival, progression-free survival, or overall survival? And the question was, do we have enough data to support that in patients with gastrointestinal cancers? Now, the article obviously goes over some review of the data available, but the core of the article was not to do a comprehensive review of ctDNA use and the evidence so far, although we used that in really putting our recommendations. So, we really had to evaluate available data. But the focus was, what are the gaps? What do we need to do? And are we ready to use ctDNA as a primary endpoint in clinical trials? Dr. Rafeh Naqash: Thank you for giving us that background. Obviously, a very broad, complicated topic with a bunch of emerging data that you've highlighted. But most importantly, for the sake of, again, trainees and listeners, could you help us understand the difference between tumor-informed and non-tumor-based ctDNA assessments? Dr. Philip Philip: Sure. So, the tumor-informed is simply meaning that you're taking the genomic makeup or the DNA fingerprint of the cancer in a given patient, and you create a profile, and then use that profile to see whether that DNA is present in the blood. So, it's very simple. It's like barcoding DNA and then going and looking for it in the blood, which means that you have to have the primary tumor. When I say primary tumor, you need to have the tumor to start off with. It doesn't really apply, maybe easily, if you just have a fine-needle aspirate and things like that. So, you really have to have a good amount of the tumor for you to be able to do that. So, that's a tumor-informed, and from the name, you can easily understand how it's done, compared to the other one, which is uninformed, whereby off-the-shelf probes are used to look for tumor DNA. And again, they're based on prior experience and prior identification of the key DNA changes that will be seen in tumors. So, that's the difference between the two in terms of the principle of the test. The uninformed will not require you to send the original tumor that you're trying to test. However, the informed, you do. The turnaround time is, again, a bit different because, as you would expect, it's shorter in the uninformed. And the reason for that, again, is the initial preparation of the profile that is going to be used in the future when you do serial testing. The sensitivity has been a bit of a discussion. Initially, people have thought that tumor-informed assays are more sensitive, more specific, more sensitive, et cetera. But in our review, we come to the conclusion saying that we don't think that's going to be a major difference. And there are obviously improvements happening in both types of assays. The sensitivities have been improving. So, at this point in time, we do feel that you have two types of assays, and we didn't feel strongly about recommending one over the other. Dr. Rafeh Naqash: Thank you for that description. You mentioned something about sensitivity, specificity. Obviously, many of us who have ordered both tumor-informed and tumor-uninformed, we understand the differences with respect to the timing. The tumor-informed one can take more time. The uninformed one, being a sort of a liquid biopsy, may not necessarily have as much of a turnaround time. Could you briefly speak to those limitations or advantages in the context of the two versions? Dr. Philip Philip: I just really want to also highlight that when we say turnaround time, so for the tumor-informed assays, the first assay that we do will be requiring a turnaround time. But once the pattern has been set and the profile has been documented, the subsequent testing doesn't require much in the way of waiting. However, when you're using this for the minimal residual disease, then you have a window of opportunity to work at. That's number one. So, it means that in patients who have resected cancer, you may end up having to wait longer than the tumor-uninformed assay, especially if you don't have easy access to your material for the baseline material to send. And also, what we'd like to do is not do the test immediately after the operation or soon after the operation. Give it some time. There's a window where you can work at, and starting minimally two weeks after the surgery. But in my experience, I'd like to wait at least four weeks just to make sure that we got an accurate reading. Sometimes when you do it very early after surgery, because of the effect of the surgery and the release of the normal DNA is also, it may dilute the tumor DNA, and then you may get a false negative. So, basically, it depends on the clinical situation. And your question is, is one better to be used than the other? I think ultimately, it ends up with the turnaround time not being as much of an issue. It might be in certain situations, depending on when you see the patients after the operation or any definitive treatment you've done and you want to look for minimal residual disease. But in general, I don't think that's going to be a real major issue. Dr. Rafeh Naqash: I remember discussing this with one of the tumor-informed platforms with regards to this barcode you mentioned. They generate a fingerprint of sorts for the tumor on the tissue, then they map it out in the blood and try to assess it longitudinally. And one of the questions and discussions we had was around the fact that most of the time, these barcoded genes are not the driver genes. If you have a KRAS mutant tumor, it's not going to be the KRAS gene that they map out. It's something that is specific. So, is there a possibility that when you are mapping out, let's say, a metastatic tumor where there is truncal and subclonal mutations at different sites, that you capture something that is not necessarily truncal, and that does not necessarily reflect some other metastatic site having a recurrence? So basically, over time, you don't see a specific mutational pattern or the signature on the tumor-informed, and then you see something on the scan which makes you think, "Well, it was not the right test," but actually it could be a different subclone or a clone mutation at a different site. Is there a concept that could help us understand that better? Dr. Philip Philip: I think you raise a very important point. Although, I have to say from my practical experience, that is not a common thing to see. In fact, for some reason, we don't see it that often in any frequency that should, at this point in time, make us concerned about the serial testing. But what you were mentioning is a real challenge which can happen. Now, the question is, how often does the clonal evolution or the divergence happen to the point that it's going to be like a false negative, is what you're saying. At this point in time, we don't really have good information on that, or any good information, practical information. And when we went through the literature and we were looking for the evidence, that wasn't something which was there clearly telling us. Although, this is something that has to be studied further prospectively. And I don't know of a study, but I might be missing it, I don't know of a study which is systematically looking at this. Although it's a very valid hypothesis and theoretical basis for it, but in real life, we still have to see how much does it really interfere with the validity of this kind of testing. Dr. Rafeh Naqash: Which brings us to the more important discussion around your manuscript. And I think that the overarching theme here is the consensus panel that you guys had recommended that ctDNA-based metrics be used as a co-primary endpoint. Could you tell us, for early-phase trials, maybe phase two studies for that matter, could you tell us what were some of the aspects that led to this consensus being formed from your working group? Dr. Philip Philip: Well, there were a number of reasons, in any order of priority, but one of them is we don't have a good sense of dynamics of the ctDNA. And again, remember this article was about gastrointestinal cancers. Maybe we know more about colon cancer, but, or colorectal cancer, but we don't know that well about the upper GI, like gastroesophageal, pancreatic, et cetera. So, we don't know what is the false negative percentages. And in fact, we know that there are certain sites of the disease, metastases, that do not lead to enough shedding of the DNA into the circulation. So, that was something else. I mean, false negativity, not knowing exactly what the dynamics are, especially in different disease types. So, that was another reason, which we felt that it may not be at this time primetime to really have those ctDNA tests as a primary endpoint. We wanted to make sure that, on the other hand, we wanted to make sure that people consider including ctDNA more like a secondary endpoint so that we can gain the information that we're lacking, at least the ones I mentioned to you. So, that was an important point of our discussions and deliberations when we were writing the article. Dr. Rafeh Naqash: And I myself have been on both sides of the aisle where - I treat people with lung cancer, you mentioned appropriately that most of the data that we have for ctDNA is generated from GI cancers, especially colorectal - on the lung cancer side, I myself had a patient with an early-stage cancer, had treatment, surgery, immunotherapy, and then had ctDNA that was tumor-informed, was positive four to five months before the imaging actually showed up. And on the other side, I've also had an individual where early-stage lung cancer, surgery, immunotherapy, and then had PET scans that showed a positive finding, but the ctDNA, tumor-informed ctDNA, was negative multiple times. So, I've seen both aspects of it, and your paper tries to address some of these questions on how to approach a negative, radiologically negative imaging but positive ctDNA potentially, and vice versa. Could you elaborate upon that a little bit? Dr. Philip Philip: Well, obviously, we do see this in practice. Again, I do GI oncology. I have patients who, you do ctDNA. I mean, my advice to anyone, when you order a test, you have to make sure that you know what you're going to do with the test, because that's the most important thing. You get a positive test, you do something. You get a negative test, you do something. But most importantly, our patients who you're following up, they are very anxious for a diagnosis they have that is not- I mean, it's cancer. If you're doing these tests, if we get continuous, repeatedly negative testing, then you really have to also tell the patient that there's a false negativity. And I mentioned to you earlier, there are certain sites of disease, like peritoneal, they may not be producing enough, or there are some tumors, their biology is such that they don't release as much to be detected in the blood. Now, one day we will get maybe a more sensitive test, but I'm talking about the tests we have now. On the other hand, if you get a positive testing, you have to make a distinction for ctDNA in the minimal residual disease situation. If you get a positive test, there is enough evidence that the patient has a worse prognosis. There's evidence for that. No one can dispute that. Again, I'm talking about colorectal cancer where there are a lot of data for that. So, in that situation, there are studies that are looking, if you get a positive test in someone who you're not intending to give any adjuvant treatment, there are studies looking into that, both in terms of intensifying, like chemotherapy, in certain patients. And also, there's work being done, if you have a negative test in someone who has stage III disease, for example, or definitely stage II disease, they may not need to give them chemo. Those things are happening. But in metastatic disease, it's a different situation. Or even in someone who has received surgery, adjuvant chemotherapy, in those patients where they, whether they're now under, in the surveillance mode, those patients, if you have a positive, it may be positive. I had a recent patient like those, eight months before we saw anything on the scans. So, the question is, if you have a positive test, is there any advantage in giving them treatment, systemic treatment? Of course, we're assuming that the PET scan is negative. So, is there really any advantage in giving someone treatment ahead of time, before you see the imaging changes? That kind of data, in my opinion, is not really available or strong. You can always think of it in different ways, explain it in different ways. It's minimal disease, maybe you get a better response. But I don't know if we really can justify at this time. Therefore, in my practice, my own practice, I do not treat just a positive ctDNA. Again, that's different than after surgery when you're thinking of whether to give adjuvant treatment, no adjuvant treatment. But someone who's finished treatments and then you're just serially monitoring the disease, those patients, I do not treat them with chemotherapy. And that was something which, based on the literature we reviewed, there was nothing out there to definitely- I mean, if you see something positive, you will do a scan earlier, you will talk to the patient, examine the patient, whatever. But if there's nothing there, starting a treatment, that's not justified at this point in time. Now, you need to do a study like that. Definitely, you need to do a study. But I can tell you that from my experience, having been involved with study design and all that, it's not an easy trial to do. It's going to be a trial- at a minimum, it will take many patients, it will take longer time to complete, and there are a number of variables there. If someone is willing to put a lot of money into it, it can be done. But I can tell you that that kind of intention to do a study like that has been very much a challenge at this time. Dr. Rafeh Naqash: Of course, as you mentioned, the follow-up time that you need for a study like that is going to be very long to get to meaningful outcomes. Dr. Philip Philip: You need to be very patient to do such a study. But the problem with a very long study is that things change, standard of care changes with time, and the assays will change. So, that's why we don't have that kind of data. I'm not sure if there are people in the community or in the academic centers who do treat based on only positive ctDNA. The other thing is that you really have to always consider the psychological impact of these tests on patients and caregivers. Sometimes it can be really very stressful, burdensome to people to sit there just waiting for the disease to show up on a scan. And therefore, in my opinion, I'm not saying definitely don't use it in that situation, I'm just saying that you have to personalize it also, to see the patient who you would like to do it and then other patients who may not do it, or you think that it's not good for them to do it. And the patient also has to understand the outcome of the test and how you're going to be interpreting it. Dr. Rafeh Naqash: That's a lot of great insights, Dr. Philip, and I know you've been involved in trial designs. I'm sure NCT and cooperative groups are actively thinking and incorporating ctDNA-based metrics as one of the endpoints in their trial. I know of a GU study that's, I think it's an Alliance study, trying to de-escalate treatment based on ctDNA. I have one of my colleagues who's also a GU investigator at OU, he's doing a ctDNA-based, tumor-informed-based de-escalation. So, obviously, more and more data, hopefully, that'll be generated in the next couple of years. Dr. Philip Philip: But remember, these studies are not using it as an endpoint. They're using it as a means of optimizing treatment, which is a bit different. So, as an endpoint, can you do a phase III trial of, let's say, a thousand patients, and your primary endpoint is not survival, but you're saying, "Can I reduce the ctDNA, clear it earlier, or whatever?" That's the sort of thing this article was about. We can't do that at this time. Dr. Rafeh Naqash: I totally understand. Thank you for explaining the difference, and hopefully more to come in this space in the next couple of years. I briefly wanted to touch upon your personal career and journey based on all that you've done and accomplished. Could you tell us about how you started, what your journey has been like, and how that connects with what you're doing right now, including mentoring other trainees and junior faculty? Dr. Philip Philip: Well, when I was in high school, I wanted to be an engineer, but I grew up in Baghdad, and all my friends wanted to do medicine, so I went with the tide, so I did medicine. I don't regret that. I would do it again if I had the opportunity. The reason why I did oncology was, I left the country and did a PhD in clinical pharmacology at the University of London. And that really got me, it was a topic which included, which was on cancer. So, I really got interested in a disease that is really a lot of science, and things are new, or were new at the time. And if I want to look back what I was doing, the beginning of my training in the 80s, second half of the 80s, and now, it's unbelievable how things have changed. But one of the things which I really have to say is that almost all my life I've been in what we call academic institutions. But I firmly believe that for people, whether academic or not, you have to be a very good, astute clinician, because many of the things we do, really, we're trying to put the patients in the center. It's not only doing fancy science, it's to do things that help the patients. And you can bring in bits and pieces of fancy science or less fancy science, but that's something which is really extremely important for us to think about, being a very good clinician, very good doctor, because medicine is a science, whether you're practicing as a solo practitioner or you're part of a large academic center. It's the way you think, the way you interrogate things that you're not sure of, the way you collaborate, the way you learn every day. I mean, at my age, I still don't like to miss any tumor board, because in each tumor board, there's something you learn, even if you think that you know everything. So, that's really the whole thing of it, is that be a very good clinician, be open-minded. Always, you have to think of things that, they look interesting, they look somehow unexplained. Always try to help find the solutions and do that. One of the major things that I feel that people should do is being also very focused on things. I mean, you have to also know what you want to do in the next 5, 10, 15 years. Because although everyone is in it in the same way when we start, but there are different things that drive people, people who want to do more of the formal research, like being an academic-like institution. But there are also a lot of people who are very successful outside of a- what we call an academic setting. In the United States, most people are not working in an academic kind of setting. Although, for me, the distinction between academic and community is getting less and less, because if you think that you do phase I trials in academia only, that's not true, because there are, in fact, in the state of Michigan, the most active phase I doctor is not even in academia, he's in private practice. So, you can do all these things. It's a matter of what you like to do, and you really have to make sure you know what you want to do. Because sometimes people are, especially early on, they get a bit confused, “What I want to do.” There's an issue of doing general oncology versus subspecialist. If you're a subspecialist doing only GI, you have to make sure that you really also have some kind of recognition that you're only a GI oncologist, recognition regional, national, international, but some degree of recognition that you feel that people are coming to you for advice as a second opinion or whatever it is. But again, you have to decide what you think you want to be, how you want to be, because there's a lot of options here between community practice, academic practice, industry, and of course, there's always the administrative thing. Some people tend to be more like going into the line of being an administrator. So, there's a lot of options for you. Dr. Rafeh Naqash: Well, thank you again, Dr. Philip, for those pearls of wisdom. I think that was very insightful. I'm sure all the trainees and early-career investigators will find all that advice very helpful. Thank you again for joining us today. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Philip Philip Disclosures Honoraria: Bayer, Ipsen, incyte, Taiho Pharmaceutical, Astellas Pharma, BioNTech SE, Novocure, TriSalus Life Sciences, SERVIER, Seagen Consulting or Advisory Role: Celgene, Ipsen, Merck, TriSalus Life Sciences, Daiichi Sankyo, SynCoreBio, Taiho Pharmaceutical Speakers' Bureau: Incyte Research Funding: Bayer (Inst), incyte (Inst), Merck (Inst), Taiho Pharmaceutical (Inst), novartis (Inst), Regeneron (Inst), Genentech (Inst), halozyme (Inst), Lilly (Inst), Taiho Pharmaceutical (Inst), merus (Inst), BioNTech SE (Inst) Uncompensated Relationships: Rafael Pharmaceuticals, Caris MPI  

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Dr. John Sweetenham shares highlights from Day 3 of the 2025 ASCO Annual Meeting, including new research for the treatment of advanced renal cell carcinoma and 2 studies on novel approaches in non-small cell lung cancer. Transcript Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 3 of the 2025 ASCO Annual Meeting. Today's selection features studies addressing the treatment of advanced renal cell carcinoma and 2 studies exploring novel approaches in non-small cell lung cancer. My disclosures are available in the transcript of this episode. The first abstract is number 4505. This study, led by Dr. Toni Choueiri of the Dana-Farber Cancer Institute, describes the final analysis of the CheckMate 214 trial, which compared the combination of nivolumab and ipilimumab with sunitinib for the first-line treatment of advanced renal cell carcinoma. The ipi-nivo combination is approved for the frontline treatment of intermediate and poor-risk advanced renal cell carcinoma based on the primary analysis of the CheckMate 214 trial, which demonstrated a higher response rate and longer overall survival compared with sunitinib. Today's presentation provided the final safety and efficacy results for the trial with long-term follow-up of more than 9 years.  The intent-to-treat (ITT) population in this trial comprised 550 patients randomized to nivo and ipi versus 546 who received sunitinib. The final analysis showed sustained long-term benefit for the combination therapy. Patients given nivolumab plus ipi had a 29% reduction in the risk for death compared with sunitinib. For patients with intermediate or poor-risk disease, there was a 31% reduction in the risk of death.   The probability of remaining in response through 8 years was more than doubled with nivolumab plus ipilimumab versus sunitinib in the ITT population at 48% versus 19%, and in the intermediate and poor-risk population at 50% versus 23%. The other important observation is that patients with favorable-risk disease appeared to have a 20% reduction in the risk for death at 9 years and more durable responses. This suggests a possible delayed benefit for ipi and nivo in this group since these differences were not seen in the earlier analysis.   No new safety signals emerged with longer follow-up, and the results confirm the use of ipi and nivo as a standard front-line combination therapy in this disease. Since this combination has been in widespread use for some years, the results are not surprising although the subgroup analysis suggesting benefit in favorable-risk patients is likely to inform practice in the future.   Today's second abstract is number is 8506, which was presented by Dr. Tony Mok from the Chinese University of Hong Kong, describing results from the phase 3 HERTHENA-Lung02 trial. This trial compared the antibody-drug conjugate patritumab deruxtecan with platinum-based chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer following a third-generation tyrosine kinase inhibitor (TKI).  Patritumab deruxtecan, also known as HER3-DXd, comprises a fully human anti-HER3 IgG3 monoclonal antibody conjugated to a topoisomerase 1 inhibitor payload, and showed activity in a previous phase 2 trial in patients relapsing after EGFR TKI and chemotherapy.   In this phase 3 study, this agent was compared with platinum-based chemotherapy in eligible patients with an EGFR-activating mutation who had previously received 1 or 2 EGFR TKIs, at least one of which was a third-generation drug, with relapse or progression after this therapy. Five hundred and eighty-six patients were enrolled, with progression-free survival as the primary endpoint.  The primary analysis showed a 9-month progression-free survival of 29% for the experimental arm compared with 19% for platinum-based chemotherapy, for a hazard ratio of 0.77 and a P value of 0.011. With higher progression-free survival rates at 6 months and 12 months, HER3-DXd also had a better objective response rate (35.2% versus 25.3%) compared with platinum-based chemotherapy (PBC), and HER3-DXd also extended intracranial progression-free survival compared with PBC in patients with brain metastases, with a hazard ratio of 0.75. Grade 3 or more treatment-related adverse events occurred in 73% of patients treated with HER3-DXd and 57% of patients who received PBC. HER3-DXd had a higher rate of grade or more 3 thrombocytopenia, and drug-related interstitial lung disease occurred in 5% of patients in the HER3-DXd arm.   The follow-up will need more time to mature since no overall survival data are currently available, but definitely an agent to watch with interest. Moving on to today's final abstract, 8500, was presented by Dr. Pasi Jänne from the Dana-Farber Cancer Institute, describing results from the phase 2 portion of the KRYSTAL-7 study. This study is exploring the use of a potent KRAS inhibitor, adagrasib, in combination with pembrolizumab in patients with advanced or metastatic KRASG12C- mutated non-small cell lung cancer.  Adagrasib has already received accelerated approval in the U.S. for previously treated locally advanced or metastatic NSCLC with a KRASG12C mutation. A previous report from the KRYSTAL-7 study demonstrated encouraging activity in combination with pembrolizumab in the frontline setting for this patient group who also had more than 50% expression of PD-L1. The presentation today described efficacy and safety data for this drug combination across all PD-L1 expression levels.  One hundred and forty-nine patients with a median age of 67 years were treated with the combination, 104 of whom had PD-L1 expression level results available, representing the so-called biomarker population in this trial. The overall response rate for the entire study population was 44%. In the biomarker population, the overall response rate ranged from 36% in those with less than 1% PD-L1 expression to 61% for those with more than 50% expression. For all patients, the median response duration was just over 26 months, and the median progression-free and overall survival rates were 11 and 18.3 months respectively.    For the biomarker population, the median progression-free and overall survival were highest in those patients with more than 50% PD-L1. No new safety issues emerged from this analysis; the most frequent toxicities were nausea, diarrhea, and increases in transaminases. Immune-related toxicities included pneumonitis, hypothyroidism, and hepatitis. These are important results and the results of the phase 3 portion of KRYSTAL-7, which compares first-line therapy with adagrasib plus pembro versus pembro alone in the KRASG12C mutated/PD-L1 more than 50% group, will be informative. For those patients with lower levels of PD-L1 expression, the authors suggest that the treatment escalation may be beneficial, possibly including the addition of chemotherapy.  That concludes today's report. Thanks for listening and I hope you will join me again tomorrow to hear more top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speaker:    Dr. John Sweetenham    Follow ASCO on social media:     @ASCO on Twitter    @ASCO on Bluesky    ASCO on Facebook    ASCO on LinkedIn     Disclosures:   Dr. John Sweetenham:    No relationships to disclose

Slovenija je ena izmed biotskih vročih točk Evrope. Kako tudi ne, ko pa naše ozemlje leži na stičišču alpske, panonske, dinarske in sredozemske biogeografske regije, zato ga zaznamujejo razgiban relief, raznovrstna kamninska podlaga ter pestre talne in podnebne razmere. Tik pred koncem maja, ko nam travniki zunaj kažejo svoj najbolj bujen obraz, se v Frekvenci X sprašujemo, zakaj so ti tako zelo pomembni za ohranjanje biotske pestrosti in kako se razlikujejo od tako imenovanih zelenih puščav. Obiskali smo nekaj rajskih travniških kotičkov na biosfernih območjih Julijskih Alp, Krasa in Kozjanskega in Obsotelja in za tokratno Frekvenco X spisali pravo senzorno razglednico z njih. Bral: Igor Velše Oddaja je bila posneta na biosfernih območjih Slovenije. V Unescov program Človek in biosfera so v Sloveniji uvrščena štiri biosferna območja: Julijske Alpe, Kras, Kozjansko in Obsotelje ter Mura. To so geološko, klimatsko in tudi kulturno raznolika območja, skupna pa so jim bogastvo biotske raznovrstnosti in navdihujoče prepletanje naravnih vrednot s kulturno dediščino.  

Broadcast from KSQD, Santa Cruz on 5-22-2025: Dr. Dawn explores groundbreaking cancer research using high-throughput "digital twin" analysis to reverse colon cancer cells back to normal states, identifying three master molecular switches that can induce normal cell differentiation without killing the cancer cells, thus avoiding traditional chemotherapy side effects. She discusses remarkable results from Memorial Sloan Kettering showing 80% of patients with mismatch repair deficient tumors, including all 49 rectal cancer patients, saw complete tumor disappearance after six months of dostarlimab immunotherapy, with no recurrence at five years and minimal side effects. The program covers innovative CRISPR applications, including targeting previously "undruggable" cancer mutations like KRAS and BRAF by selectively degrading mutant RNA messages while preserving healthy genes, offering unprecedented precision in cancer treatment. Dr. Dawn explains a clever immunotherapy approach that disguises tumors as pig organs using Newcastle disease virus carrying alpha-gal enzyme, tricking the immune system into mounting fierce attacks against cancer cells, showing promising results in both monkey and human trials. She describes fascinating research using cryoshocked tumor cells as Trojan horses, where liquid nitrogen-treated cancer cells carrying CRISPR gene editing tools directly seek out tumors, offering superior targeting compared to injecting CRISPR. The show reveals how cancers create protective acid walls around themselves to repel immune cells, with individual cancer cells pumping lactic acid away from the tumor center to form pH 5.3 barriers that kill attacking CD8 T cells within hours. Dr. Dawn discusses breakthrough mRNA cancer vaccines for glioblastoma using patients' own tumor cells, showing rapid immune system activation within 48 hours and extending survival in both dogs and humans with this aggressive brain cancer. She explores the "flower code" mechanism where cancer cells gaslight healthy cells through epigenetic manipulation, expressing dominant "flower win" codes to overpower normal cells expressing "flower lose" codes in biological turf wars. The program addresses systemic problems in cancer classification, explaining how organ-based categorization delays access to effective treatments, with patients waiting years for drugs that could help based on molecular profiles rather than tumor location. Dr. Dawn concludes by highlighting medical discrimination against people with Duffy null phenotype, primarily affecting African Americans, whose naturally lower neutrophil counts lead to reduced chemotherapy doses and excluded clinical trial participation despite no increased infection risk.

Broadcast from KSQD, Santa Cruz on 5-22-2025: Dr. Dawn explores groundbreaking cancer research using high-throughput "digital twin" analysis to reverse colon cancer cells back to normal states, identifying three master molecular switches that can induce normal cell differentiation without killing the cancer cells, thus avoiding traditional chemotherapy side effects. She discusses remarkable results from Memorial Sloan Kettering showing 80% of patients with mismatch repair deficient tumors, including all 49 rectal cancer patients, saw complete tumor disappearance after six months of dostarlimab immunotherapy, with no recurrence at five years and minimal side effects. The program covers innovative CRISPR applications, including targeting previously "undruggable" cancer mutations like KRAS and BRAF by selectively degrading mutant RNA messages while preserving healthy genes, offering unprecedented precision in cancer treatment. Dr. Dawn explains a clever immunotherapy approach that disguises tumors as pig organs using Newcastle disease virus carrying alpha-gal enzyme, tricking the immune system into mounting fierce attacks against cancer cells, showing promising results in both monkey and human trials. She describes fascinating research using cryoshocked tumor cells as Trojan horses, where liquid nitrogen-treated cancer cells carrying CRISPR gene editing tools directly seek out tumors, offering superior targeting compared to injecting CRISPR. The show reveals how cancers create protective acid walls around themselves to repel immune cells, with individual cancer cells pumping lactic acid away from the tumor center to form pH 5.3 barriers that kill attacking CD8 T cells within hours. Dr. Dawn discusses breakthrough mRNA cancer vaccines for glioblastoma using patients' own tumor cells, showing rapid immune system activation within 48 hours and extending survival in both dogs and humans with this aggressive brain cancer. She explores the "flower code" mechanism where cancer cells gaslight healthy cells through epigenetic manipulation, expressing dominant "flower win" codes to overpower normal cells expressing "flower lose" codes in biological turf wars. The program addresses systemic problems in cancer classification, explaining how organ-based categorization delays access to effective treatments, with patients waiting years for drugs that could help based on molecular profiles rather than tumor location. Dr. Dawn concludes by highlighting medical discrimination against people with Duffy null phenotype, primarily affecting African Americans, whose naturally lower neutrophil counts lead to reduced chemotherapy doses and excluded clinical trial participation despite no increased infection risk.

“A lot of other disease sites, they have some targeted therapies, they have some immunotherapies [IO]. In lung cancer, we have it all. We have chemo. We have IO. We have targeted therapies. We have bispecific T-cell engagers. We have orals, IVs. I think it's just so important now that, particularly for lung cancer, you have to be well versed on all of these,” ONS member Beth Sandy, MSN, CRNP, thoracic medical oncology nurse practitioner at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about lung cancer treatment. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by May 16, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to lung cancer treatments. Episode Notes  Complete this evaluation for free NCPD.  ONS Podcast™ episode: Episode 359: Lung Cancer Screening, Early Detection, and Disparities ONS Voice articles: Non-Small Cell Lung Cancer Prevention, Screening, Diagnosis, Treatment, Side Effects, and Survivorship Oncology Drug Reference Sheet: Amivantamab-Vmjw Oncology Drug Reference Sheet: Cisplatin Oncology Drug Reference Sheet: Lazertinib Oncology Drug Reference Sheet: Nivolumab and Hyaluronidase-Nvhy Oncology Drug Reference Sheet: Fam-Trastuzumab Deruxtecan-Nxki Optimize Your Testing Strategy and Improve Patient Outcomes With NeoGenomics' Neo Comprehensive™–Solid Tumor Assay Clinical Journal of Oncology Nursing article: Oncogenic-Directed Therapy for Advanced Non-Small Cell Lung Cancer: Implications for the Advanced Practice Nurse ONS Biomarker Database ONS video: What is the role of the KRAS biomarker in NSCLC? Biomarker Testing in Non-Small Cell Lung Cancer Discussion Tool ONS Huddle Cards: Checkpoint inhibitors External beam radiation Monoclonal antibodies Proton therapy To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “Unfortunately, because lung cancer is pretty aggressive, we'll see lung cancer mostly in stage IV. So about 50%–55% of all cases are not caught until they are already metastatic, or stage IV. And then about another 25%–30% of cases are caught in stage III, which means they're locally advanced and often not resectable, but we do still treat that with curative intent with concurrent chemoradiation. And then 10%–20% of cases are found in the early stage, and that's stage I and II, where we can do surgical approaches.” TS 2:53 “The majority of radiation that you're going to see is for patients with stage III disease that's inoperable. At my institution, a lot of stage III is inoperable. Now, neoadjuvant immunotherapy has changed that a little bit. But if you have several big, bulky, mediastinal lymph nodes that makes you stage III, surgery is probably not going to be a great option. So we give curative-intent chemoradiation to these patients.” TS 10:51 “Oligoprogression would mean they have metastases but only to one site. And sometimes we will be aggressive with that. Particularly, there's good data, if the only site of progression is in the brain, we can do stereotactic radiation to the brain and then treat the chest with concurrent chemoradiation as a more definitive approach. But outside of that, the majority of stage IV lung cancer is going to be treated with systemic therapy.” TS 15:00 “It's important for nurses to know that there's a lot of different options now for treatment. Probably one of the most important things is making sure patients are aware of what their biomarker status is, what their PD-L1 expression level is, and make sure those tests have been done. … It's good that the patients understand that there's a myriad of options. And a lot of that depends on what we know about their cancer, and then that guides our treatment.” TS 31:05

Hoe mooi had het geweest om vandaag, zeven jaar na onze eerste aflevering, nu een reportage te maken van een finale die we wél winnend afsluiten.We waren weer zo dichtbij. Maar helaas, er valt weinig te spoileren, en het terugluisteren kan pijn doen; de bekerherinneringen, het reisverslag vanuit auto en trein, de sfeerfragmenten en de almaar groeiende hoop die in de laatste minuten uiteen spat. Een nieuwe kras op onze toch al gebutste ziel. Zoals we inmiddels weten: er moet een moment komen dat de frustratie plaats maakt voor trots. En we hopen met deze aflevering stiekem een beetje daaraan bij te dragen.

In this episode, host Jonathan Sackier speaks with Alexander Spira about cutting-edge advances in lung and colorectal cancer, including EGFR and KRAS-targeted therapies. They also discuss Spira's leadership in oncology research, his thoughts on the evolving ‘town-gown' dynamic in US medicine, and his hopes for the future of cancer care.  Timestamps:  00:00 – Introduction 01:50 – Most memorable family travel adventure 03:30 – What inspired you to go into oncology 05:49 – Three recent publications in lung cancer 07:02 – Real-world data on colorectal cancer 08:15 – Sex/gender differences in non-small cell lung cancer 11:53 – The science of KRAS mutations and drug development 15:07 – Accelerating diagnostics and access to therapies 17:13 – The ‘town-gown' debate in American healthcare 18:09- Three Wishes 

Jamie from Krasl talks about a new exhibition coming to Kras later this month. Also Spring classes are starting up soon! See omnystudio.com/listener for privacy information.

“It's been known for quite a while that [KRAS] is a mutation that leads to cancer development, but for really over four decades, researchers couldn't figure out a way to target it. And so, it was often considered something that was undruggable. But all of this changed recently. So about four years ago, in 2021, we had the approval of the first KRAS inhibitor. So it's specifically a KRAS G12C inhibitor known as sotorasib,” Danielle Roman, PharmD, BCOP, manager of clinical pharmacy services at the Allegheny Health Network Cancer Institute in Pittsburgh, PA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the KRAS inhibitor drug class. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by April 11, 2027. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to KRAS inhibitors used for cancer treatment. Episode Notes  Complete this evaluation for free NCPD.  ONS Podcast™ episodes: Pharmacology 101 series Cancer Symptom Management Basics series Episode 330: Stay Up to Date on Safe Handling of Hazardous Drugs ONS Voice articles: First KRAS-Targeted Therapy Receives FDA Approval for Lung Cancer Oncology Drug Reference Sheet: Adagrasib Oncology Drug Reference Sheet: Sotorasib ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook (fourth edition) Safe Handling of Hazardous Drugs (fourth edition) ONS course: Safe Handling Basics ONS video: What is the role of the KRAS biomarker in NSCLC? ONS Targeted Therapy Huddle Card ONS Oral Anticancer Medication Learning Library ONS Oral Anticancer Medication Toolkit ONS and NCODA Oral Anticancer Medication Compass Oral Chemotherapy Education Sheets Lumakras® (sotorasib) manufacturer website Krazati® (adagrasib) manufacturer website UpToDate Lexidrug (formerly Lexicomp) To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “If we look at specifically non-small cell lung cancer, this KRAS mutation is one of the most frequently detected cancer drivers or driver mutations. It's thought that about a quarter of cases of non-small cell lung cancer have this KRAS mutation, and it's usually a specific amino acid substitution that we see in non-small cell lung cancer, so what's known as KRAS G12C mutation.” TS 2:31 “Both of these agents, sotorasib and adagrasib, have the same mechanism of action. They bind to a pocket, very specifically on the KRAS G12C protein, and they lock it in an inactive state so that it can't cause that downstream uncontrolled signaling to happen. So they're kind of shutting down the signaling, and therefore you don't get that uncontrolled cell growth and proliferation.” TS 4:27 “Another big difference to point out, and one that is often used in clinical practice to differentiate when to use these agents, is specifically adagrasib is known to have activity in patients with metastatic non-small cell lung cancer that have active brain metastases. In the clinical trial, they included patients with active brain metastases, and they found that this drug has great [central nervous system] penetration. And so it may be considered the agent of choice in patients with brain metastases.” TS 7:19 “Other considerations—I think one of the big ones—is that there are a lot of drug interactions. Just specifically calling one out that I think is pretty impactful, is sotorasib has an interaction with acid-suppressing medications. So there is the recommendation to avoid [proton pump inhibitors] and H2 antagonists in patients receiving sotorasib. They can take antacids, but you would need to space those out from their dose of sotorasib.” TS 14:14 “This needs to be a collaborative endeavor to make sure these patients are monitored appropriately. We are putting a lot of responsibility on the patients with all of this. So, again, completely administered generally in the home setting, a lot of monitoring, a lot of adverse effects, need for reporting and management—so there's a lot happening here. And it takes a team to accomplish this and to do it right. And I firmly believe that this is often a collaborative effort between our pharmacy and oncology nursing teams to make this happen. Working together to ensure outreach to patients—I think that patients are often more successful with these medications with early identification of toxicities when we're doing scheduled outreach.” TS 19:44

Conversation with Jodie Kras, Director Galleries at the Melbourne Art Fair, exploring more than a decade of her rich experience working in the bustling art scenes of Melbourne and Sydney from commercial galleries to prestigious biennales and auction houses.

Molecular differences in the profiles of low grade serous ovarian cancer (LGSOC) and high-grade SOC substantiate the need to find unique, differentiated treatment options for each epithelial ovarian cancer subtype, according to Kathleen N. Moore, MD, MS. CancerNetwork® spoke with Moore, Virginia Kerley Cade Endowed Chair of Cancer Development, associate director of Clinical Research at the Stephenson Cancer Center, director of the Oklahoma TSET Phase I Program and professor in the Section of Gynecologic Oncology the University of Oklahoma Health Sciences Center, about distinguishing low grade serous ovarian cancer from other types of ovarian cancer, current treatment options and clinical trials evaluating new regimens, as well as managing treatment in younger patients with or those seeking to preserve fertility. Moore began by differentiating LGSOC from high grade SOC, stating that this disease typically occurred in younger patients and was primarily characterized by MAP kinase alterations, specifically KRAS and BRAF mutations. She then discussed the emergence of endocrine therapies in this indication owing to the presence of estrogen receptors. Additionally, first line treatment was discussed, with the standard of care defined by primary cytoreduction followed by paclitaxel and carboplatin. She then highlighted multiple clinical trials assessing alternative treatment in this indication, particularly involving the use of letrozole (Femara). Other clinical trials evaluated the use of CDK4/6 inhibition plus fulvestrant or BRAF and MEK inhibition with letrozole, with Moore emphasizing the potential for these studies to shift the treatment paradigm in the frontline setting. Furthermore, she suggested that CDK4/6 inhibition may help enhance responses in patients with recurrent LGSOC. Moore then highlighted treatment concerns for younger patients and those seeking to preserve fertility, while expressing the importance of understanding a patient's goals, which may help optimize outcomes. She concluded by reiterating the importance of designing trials and tailoring treatment considering the molecular profile of LGSOC.

Dr Fakih discusses the significance of this approval, key findings from the pivotal CodeBreaK 300 trial (NCT05198934), and how this combination fits into the current KRAS G12C–mutated mCRC treatment paradigm.

In a conversation with CancerNetwork®, Marwan G. Fakih, MD, spoke about the FDA approval of sotorasib (Lumakras) plus panitumumab (Vectibix), and how it may affect the treatment paradigm for patients with KRAS G12C-mutant metastatic colorectal cancer (CRC). Fakih is a professor in the Department of Medical Oncology & Therapeutics Research, associate director for Clinical Sciences, medical director of the Briskin Center for Clinical Research, division chief of GI Medical Oncology, and co-director of the Gastrointestinal Cancer Program at City of Hope Comprehensive Cancer Center in Duarte, California. According to Fakih, the approval of this combination regimen is a “welcome step” for those with metastatic CRC harboring KRAS G12C mutations. Based on supporting data from the phase 3 CodeBreaK 300 trial (NCT05198934), sotorasib/panitumumab may prolong progression-free survival (PFS) and reduce disease burden in patients while offering improvements in other outcomes vs prior standards of care (SOC) like trifluridine/tipiracil (Lonsurf) and regorafenib (Stivarga). Topline data at the time of the approval showed a median PFS of 5.6 months (95% CI, 4.2-6.3) with sotorasib at 960 mg plus panitumumab vs 2.0 months (95% CI, 1.9-3.9) in the SOC arm, in which patients were assigned to receive trifluridine/tipiracil or regorafenib (HR, 0.48; 95% CI, 0.30-0.78; P = .005). Additionally, the overall response rate was 26% (95% CI, 15%-40%) vs 0% (95% CI, 0%-7%) in each respective arm. Looking ahead, Fakih highlighted the potential next steps for research associated with the sotorasib combination as well as other novel therapeutic strategies in the gastrointestinal cancer space. For example, he described the phase 3 CodeBreaK 301 study (NCT06252649), which will evaluate sotorasib/panitumumab as frontline therapy when administered in combination with folinic acid, fluorouracil, and irinotecan (FOLFIRI) vs FOLFIRI plus bevacizumab (Avastin) in metastatic KRAS G12C-mutant CRC. Other novel agents under development in the space include RAS inhibitors and immunotherapy regimens combining CTLA-4 inhibitors with anti–PD-L1 agents. References 1. FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. News release. FDA. January 16, 2025. Accessed February 12, 2025. https://shorturl.at/1WviB 2. Kim TW, Price T, Grasselli J, et al. A phase 3 study of first-line sotorasib, panitumumab, and FOLFIRI versus FOLFIRI with or without bevacizumab-awwb for patients with KRAS G12C–mutated metastatic colorectal cancer (CodeBreaK 301). J Clin Oncol. 2025;43(suppl 4):TPS326. doi:10.1200/JCO.2025.43.4_suppl.TPS326

Michelle was diagnosed with Stage 3a Adenocarcinoma of the lung in 2011 with the KRAS mutation and is still alive and living well. ORDER MY NEW BOOK SWEET INDULGENCE!!! https://www.amazon.com/Chef-AJs-Sweet-Indulgence-Guilt-Free/dp/1570674248 or https://www.barnesandnoble.com/w/book/1144514092?ean=9781570674242 GET MY FREE INSTANT POT COOKBOOK: https://www.chefaj.com/instant-pot-download MY BEST SELLING WEIGHT LOSS BOOK: https://www.amazon.com/dp/1570674086?tag=onamzchefajsh-20&linkCode=ssc&creativeASIN=1570674086&asc_item-id=amzn1.ideas.1GNPDCAG4A86S Disclaimer: This podcast does not provide medical advice. The content of this podcast is provided for informational or educational purposes only. It is not intended to be a substitute for informed medical advice or care. You should not use this information to diagnose or treat any health issue without consulting your doctor. Always seek medical advice before making any lifestyle changes. Bio: Dr Dana Simpler is a primary care doctor who practiced in Baltimore City until retirement in 2022. She is a graduate of University of Maryland Medical School. She became interested in Lifestyle Medicine after reading The China Study by T. Colin Campbell and Prevent and Reverse Heart Disease by Caldwell Esselstyn. After attending many Lifestyle Medicine conferences geared towards practitioners, she incorporated diet and lifestyle recommendations into her regular medical practice. "I found diet changes had a great impact on my patient's health. While not everyone is open to change, it is important for people to at least be advised what they can do to prevent or reverse their medical conditions."

JCO PO author Dr. Hatim Husain at University of California San Diego, shares insights into his JCO PO article, “Adagrasib Treatment After Sotorasib-Related Hepatotoxicity in Patients With KRASG12C-Mutated Non–Small Cell Lung Cancer: A Case Series and Literature Review”, one of the top downloaded articles of 2024. Host Dr. Rafeh Naqash and Dr. Husain discuss how to utilize real-world and clinical trial data to discern the safety of adagrasib (another KRASG12C inhibitor), following sotorasib discontinuation due to hepatotoxicity. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we bring you engaging conversations with authors of clinically relevant and highly significant JCOPO articles. I'm your host, Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Assistant Professor at the OU Stephenson Cancer Center.  Today, I'm very excited to be joined by Dr. Hatim Hussain, Professor of Medicine at the University of California, San Diego, and author of the JCO Precision Oncology article, “Adagrasib Treatment After Sotorasib-Related Hepatotoxicity in Patients With KRAS-G12C-Mutated Non-Small Cell Lung Cancer: A Case Series and Literature Review.” This was one of the top downloaded articles of 2024. And the other interesting thing is we generally don't do podcasts for case reports or case series, so this is one of the very few that we have selected for the podcast.  And at the time of the recording, our guest disclosures will be linked in the transcript.  Dr. Hussain, welcome to our podcast and thank you for joining us today. Dr. Hatim Husain: Thank you Dr. Naqash. Such a pleasure to be here and to speak with you all. Dr. Rafeh Naqash: And for the sake of this podcast, we'll refer to each other using our first names. So again, as I mentioned earlier that this is one of the very few case reports that we have selected for podcasts in JCOPO and the intention was very deliberate because it caters to something that is emerging where we are trying to treat more KRAS mutant patients with different KRAS inhibitors. And you tried to address one very unique aspect of it in this article which pertains to toxicity, especially hepatotoxicity. So for the sake of our listeners who tend to be community oncologists, trainees, academic faculty, can you tell us what are KRAS inhibitors? What is KRAS-G12C? And how do some of these approved KRAS inhibitors try to inhibit KRAS-G12C? Dr. Hatim Husain: Sure. For a long time actually we've not had a selective way to inhibit mutant KRAS. And over the last several years actually now, we've seen some dramatic advances here, particularly with the FDA approval of some of the selective inhibitors against the G12C variant. So KRAS-G12C is an isoform of KRAS that is most common in lung cancer and in fact actually is a transversion mutation in the KRAS gene that is a product of the carcinogen of tobacco. And in fact, the incidence of KRAS-G12C in lung cancer, it's quite astounding where as many KRAS-G12C patients there are, there can be, as you know, more than EGFR patients in certain populations and cohorts. The medicines sotorasib and adagrasib were rationally designed to be selective KRAS-G12C inhibitors. And the way that they do this is that they lock the KRAS protein in the OFF state. KRAS is a protein that oscillates between an ON and an OFF state and by virtue of locking the protein in an OFF state, it has shown inhibition of downstream signaling and mitigation of tumor growth and, in fact, tumor cell death. Dr. Rafeh Naqash: I absolutely love the way you describe the ON and OFF state, the oscillation where the ON is bound to the GTP and the OFF is bound to the GDP. The two KRAS inhibitors as currently FDA approved, as you mentioned, are RAS OFF inhibitors and they're emerging KRAS inhibitors that are RAS ON. So now, as we have known from previous data related to immunotherapy and EGFR TKIs such as osimirtinib where toxicity tends to be a compounded effect when you have osimertinib given within a certain timeline of previous checkpoint therapy, we've seen that in the clinic as the data for these KRAS inhibitors is emerging, you talk about some very interesting aspects and data about what has been published so far with regards to prior use of immunotherapy or chemo immunotherapy and the subsequent use of KRAS inhibitors. Could you elaborate upon that? Dr. Hatim Husain: Sure. So for this population of patients, the first line approved strategy is a strategy that most cases will incorporate immune therapy and chemotherapy. Immune therapy can have some important responses for patients with KRAS-G12C. This may be due to the fact that KRAS-G12C patients may have a higher incidence of prior smoking, perhaps higher mutation burdens in some patients, and perhaps immunogenicity is defined in that context. So the standard of care in the first line currently includes immune therapy or immune therapy and chemotherapy. Where the current FDA approvals for selective G12C inhibitors are are after the first line of therapy. There are a number of trials exploring these medicines in the first line to see if they may be incorporated into a future treatment paradigm. Dr. Rafeh Naqash: Thank you for that explanation. Now, going to what you published in this manuscript, can you help us understand the context of why you looked at this? Even though the data just comprises a case series of a handful of patients, but the observations are very interesting and these are real world scenarios where we often tend to be in situations where an individual has had toxicity on a certain drug and may have some response to that drug, but at the same time, the toxicity is challenging. And then you try to debate whether another drug in the same class might be beneficial without those toxicities. So you've tried to address that to some extent using this data set. So can you elaborate upon the question, the methodology, what you tried to look at, and important observations that you have? Dr. Hatim Husain: Yes, our paper was actually inspired by one of my patients. My patient was a patient who had received chemotherapy and immune therapy and actually in the past, even, you know, additional lines of immune therapies, it was really coming to the edge of where standard treatments would exist. It was right at the same time that these selective inhibitors had been approved and the patient had received sotorasib. And what was remarkable was, when given sotorasib, patient had a very high peak and spike in the transaminases. And we would do different trials of strategies around dose, around interruptions. And it was becoming quite difficult, actually, for the patient to proceed with additional therapy. It was around similar times, actually, and I do want to make a note that the patient was progressing, driven in large fact by the fact that we've had to interrupt the medicine. So we feel and believe that the patient had had inadequate dosing because of the level of toxicity that the patient was having with transaminase increase. So it was around the same time that adagrasib was first commercially available that we were at that point, and we did a trial of adagrasib post-sotorasib, largely driven by necessity, without having additional options to provide this patient in our environment. What was remarkable was when the patient received the adagrasib, there were no spikes in transaminases similar to what we had seen before. And that really led us thinking and to say, “Is this adverse event of transaminase increase or hepatotoxicity, is this a class effect with KRAS-G12C inhibitors, or is it more nuanced than that? Are there different, perhaps, mechanisms by which the medicines may work that may more or less differentially contribute to this adverse event?” And so that inspired us to kind of do a larger analysis, kind of really reach out to a larger network of physicians to gather insights and to gather responses in patients who had had a serial approach of sotorasib and then adagrasib.  What we found in this process was, in fact, actually there were many more cases of patients who resembled my patient, where the sequence of sotorasib going to adagrasib may have demonstrated differential contribution of hepatotoxicity in that context. And that really motivated us to put the publication together to due diligence, and in the publication spend a lot of time to kind of outline each patient case in detail around metrics surrounding time from last immune therapy, the number of days on sotorasib, the best response to sotorasib, the interval between sotorasib and adagrasib, the duration of adagrasib and then the grade of hepatotoxicity seen in each of the contexts, and particularly kind of the adagrasib and patient disease status as well. We were quite inspired by the effort to try to, if we do not have randomized data in comparison of one medicine to another, which we do not at this juncture, we do not have a randomized analysis to really diligently and rigorously compare the rates of AEs across each medicine, and even in sequence, we do not have that with immune therapy. But what we felt was trying to get more analysis of this sequential approach of, if patients had received a medicine, had to be taken off because of toxicity and then actually tried on a new medicine, what were those rates? We felt like that was at least some information to try to get at this question. Dr. Rafeh Naqash: And you bring forward a very important point, which is, a lot of times in the real world setting we don't have cross trial comparisons that can be fully applicable, or we don't have trials that compare two drugs of the same class with respect to the AE profile or efficacy. And observations like the one that you described that led to this study are extremely critical in trying to help answer these questions.  From a data standpoint, and you allude to it to some extent in your manuscript, the trials that are trying to address combination of KRAS-G12C with immunotherapy, especially sotorasib or adagrasib, can you elaborate on that data, what has been published so far and summarize it for our listeners? Dr. Hatim Husain: So there is data from clinical trials looking at patients actually who have received concomitant immune therapy and sotorasib. What was seen in this, in a real world analysis, was that some patients actually who had received sotorasib within a close proximity of immune therapy, as well as a larger study actually which showed in combination there were higher rates of hepatotoxicity in that context. In fact, there were rates of grade 3 hepatotoxicity. And I think built upon that data there's a recognition in the field that we have to be very diligent in terms of even the clinical trial designs in how to understand the pairing between immune therapy and selective G12C inhibitors. There are many trials that are ongoing, one of the studies that is ongoing is known as the KRYSTAL-7 study, which is evaluating adagrasib in combination with pembrolizumab in the first line. And we await more information on that strategy as well. In the context of sotorasib, because of some of the trials that have shown higher rates of hepatotoxicity, there are some additional trials now looking at sotorasib in combination with chemotherapy, and those also have some information that have been reported as well. Dr. Rafeh Naqash: From a drug development standpoint, as you mentioned, there's always a tendency to combine something with something else. And in my practice, and I'm sure in your practice too, when we do early phase trials, many trials are still focused on choosing the maximum tolerated dose, which may be something that we need to gradually move away from as we try to implement these combinations of multiple antibodies plus some of these target agents from maybe the biological optimal dose rather than the maximal tolerant dose is a better way to look at the drugs, the pharmacokinetic profile, and then see what is likely the safest combination with the most appropriate target engagement. Do you have any thoughts on that or insights on that from a drug development perspective? Dr. Hatim Husain: It's a wonderful question and I think it is a very insightful question and understanding of where we are in space right now. And I agree with you that historically, cancer drug development was really hinged upon medicines that perhaps required higher doses to see a benefit or to inch out kind of marginal increases upon where we were at. Now, in combination with medicines that have non-overlapping mechanisms of action, the concept is: Can there actually be more synergy across an approach using combinatorial strategies rather than just additive effects? And I think that in some cases this is being studied with immune therapy, in some cases actually even in the context of other novel mechanisms for cancer therapy. I think that in my practice, I will really try to see how a patient at an approved dose will respond. But definitely I'm open to the concept that there may be a dose that doesn't have to be the maximally tolerated dose, but rather the dose that responses can be seen and perhaps actually at a lower dose than what drives many toxicities. Dr. Rafeh Naqash: I often describe this to my patients as individual patient dose optimization outside of a clinical trial, where I'm sure you've probably done this, where in older adults maybe a lower dose of osimertinib is tolerated better, or a lower dose of sotorasib or adagrasib for that matter, tolerated better with perhaps a similar level of efficacy, since we don't have comparisons between doses and efficacy so far.  So I think in the bigger picture, as we discussed in a nutshell, what I would really like the listeners to understand is as we try to move towards this field of precision medicine targeting more and more of the undruggable genes, there's bound to be a certain level of toxicity patterns that we'll start observing. So I think these real world scenarios which may not be addressed using clinical trials because it is in the real world setting where you cycle one treatment after another after another, which may or may not be allowed in most trials and the real world setting can inform, in certain cases, subsequent trial designs. So I think the most important message, at least that I took from your manuscript, was that these real world observations can make a huge difference and inform practice, even though the data sets may be small. Of course, you want to validate some of these findings in a bigger, broader setting, but proof of concept is there. And I think next time I see an individual in my clinic where I see better toxicity, I'll definitely try to talk to them about subsequent treatment with another KRAS inhibitor, maybe adagrasib or something else, if and when appropriate.  Do you have any closing thoughts on some of these things that we discussed? Dr. Hatim Husain: I just want to leave the audience actually with this concept that sometimes we group targeted therapy side effects as being class effects unanimously. And I do think actually that each inhibitor may have different off target effects on where medicine may act. We don't truly understand the mechanism of hepatotoxicity in the context of selective KRAS-G12C inhibitors. One of the hypotheses may be due to off target cysteine reactivity in the numerous off target binding sites that certain medicines may have over others. And just even qualitatively which off target binding sites there may be, and how that may lead to either immunogenic responses and other organs or such. So I do think that we do need more research to understand the mechanism. But I think where we are at right now in this space is not assuming that all medicines are going to have the exact same toxicity. I think especially when patients may not have other options, this is something to consider as well. Dr. Rafeh Naqash: Thank you so much. Now, outside of the scientific insights, Hatim, I know you a little bit from before. And knowing the kind of work that you've done in precision medicine, I'm really interested to know about where you started, how you started, how things have been, and what kind of advice you have for junior faculty fellows who are interested in this field of precision medicine that is becoming more and more exciting as we progress in the oncology space. Dr. Hatim Husain: Thank you, Rafeh. I will say, actually as a medical student, I was actually very interested in oncology, partly because it was then and still remains one disease or a constellation of diseases that just has such a high psychological burden on patients. And through the experiences I've had, I really can understand and relate with that concept. I did my medical school at Northwestern, residency at the University of Southern California, and then my oncology fellowship at Johns Hopkins University.  And now I've been on faculty at University of California, San Diego, for about 12 years now. It's been a great experience paralleled with the fact that during these last 12 years, I've really seen how the developments in precision oncology, both targeted therapy as well as immune therapy, have really blossomed and unfolded. A large area of my research in my career has kind of focused on cancer genome and integration of novel technologies to really see how they may have clinical application. When I was in my fellowship and as a young faculty, the liquid biopsy was actually coming into development. And this was hinged upon information that had come forward in the prenatal space where some patients actually who were undergoing prenatal testing during pregnancy were found to have complex karyotypes and genomic alterations and then retrospectively found to have cancer.  And doing my fellowship at Johns Hopkins, some of the pioneers in liquid biopsy were my mentors and really kind of instilled in me that passion for really thinking through how cancer genomics can be integrated through time. And some of the research that I have been doing has been looking at clonal evolution of cancer, how cancer is changing over time, and how we can think through the right surveillance strategies to really understand how that change is occurring. The dynamics of ctDNA in retrospective cohorts have been studied and shown that, you know, there can be associations between progression-free survival and other clinical endpoints. The current paper that we are speaking about parallels that in a certain way where, rather than say, looking at clonal evolution and say, the efficacy answer of sotorasib first and then adagrasib and how frequently can adagrasib salvage patients, this looks at it from a different angle around toxicity. And I think that is a key point because, at my core, I really do enjoy the clinical aspect of complex decision making on behalf of patients weighing efficacy and toxicity that they may have as they try to get the best quality of life through this journey. Dr. Rafeh Naqash: Thank you again, Hatim, for all those insights, both from the scientific perspective as well as personal perspective. We appreciate that you chose JCOPO as the destination for your work.  And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Hatem Husain Disclosures Consulting or Advisory Role: AstraZeneca, Foundation Medicine, Janssen, NeoGenomics Laboratories, Mirati Speakers' Bureau: AstraZeneca, Janssen Institution Research Funding: Pfizer, Bristol-Myers Squibb, Regeneron, Lilly Travel, Accommodations, Expenses: AstraZeneca, Janssen, Foundation Medicine  

Accountability. It's a word that can make people squirm, but if you want to see real transformation in your business, you need to embrace it.Today on The Chris LoCurto Show, we're unpacking how accountability creates clarity, aligns teams, and strengthens leadership.We'll cover the essential tools you need to build a culture of accountability and walk through practical strategies to implement it effectively.So if you're ready to learn how to hold your team accountable in a way that fosters growth—without feeling like the bad guy—this episode is for you. Let's dive in.Episode Timestamps and Key TakeawaysAccountability Aligns Teams to Vision, Mission, and Strategy (00:05:47)Discover how accountability keeps your team aligned with the company's mission, vision, and strategy, ensuring everyone moves in the same direction efficiently.Clarity Through KRAs and KPIs (00:12:07)Learn how KRAs and KPIs provide measurable clarity, setting clear expectations for every role and eliminating confusion in performance evaluation.The Power of Structure and Organization (00:20:19)Explore why structured systems, meeting rhythms, and project management tools enhance accountability and reduce miscommunication.High-Quality Communication Builds Trust and Clarity (00:23:35)See how effective communication fosters trust, strengthens relationships, and ensures alignment within your team.Next-Level Leadership LIVE Event 2025 (00:26:46)Get details on our upcoming event in April, where we'll equip you with leadership tools to reduce overwhelm and lead with confidence. Learn more.Coaching, Training, and Supporting Success (00:30:25)Understand how ongoing coaching and training set your team up for success, ensuring accountability becomes a tool for growth rather than micromanagement.Action Items to Build Accountability (00:34:32)Practical steps to implement accountability in your business, from documenting KRAs to fostering open communication and using project management tools.Additional Resources (00:36:29)Related podcast episodes that dive deeper into accountability and communication strategies.Conclusion (00:37:21)Accountability isn't about micromanaging—it's about clarity, alignment, and empowerment. When your team understands their roles, expectations, and goals, they perform at a higher level.Start implementing these strategies today and watch your business transform.If this episode resonated with you, hit that like button, leave a review, and share it with others who need to hear it.Take this information, change your leadership, change your business, and change your life. See you next time!

BUFFALO, NY - February 18, 2025 – A new #researchpaper was #published in Oncotarget, Volume 16, on February 12, 2025, titled “Could Panitumumab with very low dose Capecitabine be an option as a maintenance regimen." In this study, researchers Doaa A. Gamal, Aiat Morsy, and Mervat Omar from Assiut University Hospital, evaluated a new maintenance treatment for metastatic colorectal cancer (mCRC). Their findings suggest that a combination of two drugs—Panitumumab, a targeted therapy that blocks a protein called epidermal growth factor receptor to slow cancer growth, and low-dose Capecitabine, a chemotherapy drug that converts into 5-fluorouracil (5-FU) inside the body to stop cancer cells from growing and dividing—could help extend survival in patients with mCRC. This regimen appears to be both effective and well-tolerated, especially for patients with wild-type KRAS mCRC who had previously responded to treatment. Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Standard treatment often involves a combination of chemotherapy and targeted therapies, but many patients face challenges related to treatment toxicity and resistance, which can lead to treatment interruptions. This study tested whether a lower-intensity maintenance treatment could help keep the cancer under control after initial treatment. The study involved 25 mCRC patients with wild-type KRAS and BRAF, who first received six rounds of standard 5-FU-based chemotherapy with Panitumumab. Patients who responded well then switched to a maintenance treatment of Panitumumab every two weeks and a low, continuous dose of Capecitabine. The results showed that patients had a median progression-free survival of 18 months and a median overall survival of 45 months, indicating a strong potential benefit. Patients with metastases detected at the same time as the primary tumor showed a longer progression-free survival than those with metastases appearing later. The treatment was also well tolerated, with only 8% of patients experiencing severe side effects such as skin rash or diarrhea, which were managed with standard treatments. "In our research, the toxicity profile was very acceptable, and no patients needed to stop treatment or had a dose modification due to toxicity." Finding a way to keep cancer under control while reducing side effects is a major goal in cancer treatment. While other maintenance therapies like Bevacizumab and Cetuximab have been studied, this research suggests that Panitumumab with low-dose Capecitabine could be a promising new option. Panitumumab is already an FDA-approved drug, but its role in maintenance therapy had not been extensively explored. The results of this study suggest that this combination may help delay disease progression while keeping side effects manageable, ultimately improving patients' quality of life. Although larger studies are needed, these findings open the door for further clinical trials to confirm the benefits of this regimen. If validated, this approach could change the standard of care for mCRC patients, particularly those who cannot tolerate more intensive chemotherapy. DOI - https://doi.org/10.18632/oncotarget.28687 Correspondence to - Doaa A. Gamal - doaaalygamaal@gmail.com Video short - https://www.youtube.com/watch?v=wuPSS0EdK-8 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

Featuring articles on asymptomatic severe aortic stenosis, kidney disease, fracture prevention in women, and residual breast cancer, the future of the U.S. physician workforce, mutant KRAS signaling, and manufactured chemicals and children's health; a review article on the identification and treatment of alcohol use disorder; a case report of a man with loss of consciousness and a fall; and Perspectives on striking a balance, on changing Medicare payment to strengthen primary care, and on Schrödinger's cancer.

In this episode, we explore how Key Result Areas (KRAs) are more than just management tools—they're the foundation of a well-run business.KRAs bring clarity, align roles with company goals, and eliminate confusion, helping your team achieve greater productivity and success.If you're ready to streamline your leadership and business processes, this episode is packed with actionable insights, examples, and strategies to help you use KRAs effectively.Episode BreakdownWhat KRAs Are and Why They Matter (00:01:30)KRAs define expected results for each role, creating clarity for both leaders and team members. Discover why they're essential to avoid misalignment and confusion, with examples for various roles.The System Approach to KRAs (00:04:45)KRAs tie directly to your mission, vision, and strategy. Learn how aligning roles with business goals ensures everyone moves in the same direction, illustrated with StratPlan examples.Next-Level Leadership LIVE Event (00:09:26)This April 2-4, join us for three transformative days to learn actionable leadership strategies, reclaim work-life balance, and connect with leaders who share your challenges and goals.How KRAs Prevent Leadership Struggles (00:14:03)Unclear roles lead to shifting expectations and wasted resources. KRAs solve this by providing measurable goals and accountability, ensuring your team operates efficiently.Integrating KRAs into Your Leadership Strategy (00:16:35)Discover how to create KRAs that tie team objectives and KPIs to company success, reducing tough conversations and improving results.Why Revisiting KRAs Is Critical (00:20:09)Regularly reviewing KRAs ensures clarity and growth. Learn a simple process for monthly reviews to keep your team aligned and productive.Additional Resources (00:22:58)For a deeper dive into KRAs, check out Episode 120 (The What, Why, and How of KRAs) and Episode 406 (What Good is a KRA?), available on chrislocurto.com.Final ThoughtsWhether you're new to KRAs or need a refresher, this episode gives you the tools to bring clarity and alignment to your team. Share this episode with a fellow leader and join us for the Next-Level Leadership LIVE Event in April!Take this information, change your leadership, and change your life. See you next time!

In today's episode, we had the pleasure of speaking with Alec Watson, MD, a thoracic oncology fellow in the School of Medicine in the Division of Medical Oncology at the University of Colorado Anschutz Medical Campus in Aurora. In our exclusive interview, Dr Watson discussed the rationale for and key findings from a retrospective analysis examining the ways that oncogene overlap could identify clinically relevant thresholds for MET, KRAS, and HER2 gene copy number gain in non–small cell lung cancer; next steps for this research; and the future implications of these findings.

Welcome to The Chris LoCurto Show! As we kick off the new year, instead of chasing new strategies, let's focus on resetting and recommitting to the essentials that drive success.In this episode, I'm sharing actionable steps to help you align your team, elevate your leadership, and make 2025 your strongest year yet. Let's dive in!Recommit to Discipline in Leadership (00:01:20)Consistency is key. Reset your meeting structures to align your team, ensure accountability, and boost productivity. Examples of effective meetings are shared.Get Out of the Leadership Crazy Cycle (00:05:27)Stop firefighting and start delegating effectively. Tools like the delegation matrix can help you focus on what truly matters.Next-Level Leadership LIVE Event 2025 (00:08:57)Join us April 2-4 for a transformative leadership event. Learn strategies to lead smarter, reclaim your personal life, and connect with like-minded leaders.Engage with Your Business's Financial Health (00:13:40)Dive into your financials! Regularly reviewing your P&L statements, budgets, and forecasts is crucial for making informed decisions.Reevaluate Your Team Communication (00:17:24)Clear expectations and consistent communication prevent accountability gaps. Regular one-on-ones help align your team with your goals.Focus on Accountability and Ownership (00:21:22)Tough conversations become easier with strong accountability. KRAs provide clarity and measurable results to keep your team on track.Action Items (00:25:05)Audit your leadership practices, hold regular meetings, commit to financial reviews, and delegate strategically. Start small and build momentum.Additional Resources (00:27:20)Dive deeper with episodes:532 | Three Rules for Leading Effective Meetings430 | Building Predictability Into Your Business Finances – Part 1120 | KRA: The What, The Why, and The How of Key Result Area523 | How To Kill The Leadership Crazy CycleReflect on one area where you can reset and recommit. Let's lead boldly into 2025!

Welcome to The Chris LoCurto Show! Today, we're diving into a vital topic for leaders: how to build a team that operates without you. If stepping away from your business feels impossible, or if your team relies on you for every decision, this episode is for you.We'll explore the power of delegation, empowering your team, training, and building clarity in mission, vision, and KRAs—all foundational to creating a self-sufficient team. This is part one of a two-part series, so let's dive in!Episode Breakdown1. Introduction (00:00:00)Set yourself free by building a team that thrives independently and elevates your leadership to the next level.2. Next-Level LIVE Event 2025 (00:04:25)Discover practical tools to lead smarter and achieve work-life balance while growing your business.3. Delegation Is Key to an Independent Team (00:09:27)Proper delegation isn't just handing out tasks; it's about giving your team clear expectations, tools, and autonomy to succeed.4. Stop Micromanaging and Start Empowering (00:16:16)Micromanagement kills creativity. Empower your team to solve problems with actionable techniques to foster independence.5. Training and Development – The Gift That Keeps on Giving (00:23:18)Continuous training grows your team's capabilities and aligns them with your mission and vision for long-term success.6. Building Leaders Within Your Team (00:28:51)Developing leaders within your team creates stability and allows you to focus on bigger-picture priorities.7. Clarity in Mission, Vision, and KRAs – No Guesswork (00:35:03)Clarity eliminates confusion—align your team with your mission, vision, and KRAs to keep them on track.8. Making KRAs Work for Your Team (00:37:26)KRAs ensure accountability and smooth operations; grab the free KRA sample linked in the show notes to get started.9. Additional Resources (00:37:59)Check out Episodes 234 (Why You and Your Team Need KRAs) and 555 (Acing Your Goals and Establishing Processes With Your Team) for deeper insights.This is just the beginning of creating a self-sufficient team. Next time, we'll explore cultural communication and accountability systems that hold everything together. Don't miss it!

The OSUCCC -James is a leader in the treatment of pancreatic cancer, with the utilization of robotic Whipple surgery, the use of chemotherapy and radiation before surgery, multiple clinical trials designed to find even better ways to treat patients and a large multidisciplinary pancreatic cancer clinic.“We're always thinking about what's the next step and about the patient of tomorrow, that's a huge driver,” said Susan Tsai, MD, MHS, a surgical oncologist who specializes in pancreatic cancer and is Director of the OSUCCC – James Division of Surgical Oncology. “The pancreas helps regulate blood sugars and also helps you digest food,” Tsai explained, adding that it's hard to diagnose, which means patients often come to her with later-stage cancer. “In 70 to 80 percent of the patients we see, they will have recurrent disease somewhere else in their body,” Tsai said, adding this statistic has led to a new way to treat patients. “In the old days we'd often rush patients to surgery to remove the cancer as quickly as possible, but because the recurrence rates were so high maybe that isn't the best way to treat patients. Now, we utilize systematic therapy [chemotherapy and radiation] upfront, before surgery and we're seeing better results.” The development of robotic Whipple surgery to perform the complex and invasive pancreatic cancer surgery is another innovation. Using previous surgical techniques “there was about a 30 percent mortality rate,” Tsai said, adding the advances of the less-invasive and more precise Whipple surgery “practiced at a high-volume comprehensive cancer center such as the James have reduced that to less than 3 percent.” To date, pancreatic cancer has not been a good target for immunotherapy. “Now, we have been able to target a genetic mutation, called KRAS, a gene that drives many different types of cancer,” Tsai said, adding clinical trial are now testing drugs that appear to be able to target KRAS and enable the immune system to recognize and attack them. In another, soon-to-open clinical trial in which Tsai helps lead, the molecular profile of a biopsy of a patient's pancreatic cancer is analyzed to determine which chemotherapy drug to utilize. “This could be a great resource for patients,” Tsai said.

BUFFALO, NY - November 4, 2024 – A new #casereport was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “A case of adenosquamous pancreatic cancer with a KRAS G12C mutation with an exceptional response to immunotherapy.” This case report highlights a remarkable and unexpected response to immunotherapy in a patient with metastatic adenosquamous pancreatic cancer (ASCP), a rare and aggressive form of pancreatic cancer. The study, led by Murtaza Ahmed, Brent K. Larson, Arsen Osipov, Nilofer Azad, and Andrew Hendifar from Cedars-Sinai Medical Center and Johns Hopkins University, provides new hope for ASCP patients, who are traditionally underserved by current treatment options. The team documented a 68-year-old male with metastatic ASCP carrying a KRAS G12C mutation. Unexpectedly, after limited success with standard therapies, the patient's cancer responded significantly to pembrolizumab, a type of immune checkpoint inhibitor, despite the absence of typical markers indicating suitability for immunotherapy. Pancreatic cancer remains one of the most lethal cancer types, with few advancements in effective treatments for its rarer forms, such as ASCP, which accounts for only 1-10% of all pancreatic cancer cases. Traditionally, ASCP has been treated with chemotherapy based on protocols for the more common pancreatic ductal adenocarcinoma, despite the distinct tumor characteristics. This case suggests that ASCP's unique tumor microenvironment may make it more receptive to immunotherapy. Researchers are hopeful that this new understanding will drive clinical trials focused on immunotherapy specifically for ASCP patients, potentially offering new options for those with limited treatment success. “To that point, there is an active multi-center phase 2 trial investigating outcomes and responses to ICI in patients with metastatic or unresectable ASCP or ampullary cancer.” In conclusion, this report signals a potential shift in the treatment of rare and aggressive pancreatic cancer subtypes like ASCP. As oncology increasingly embraces personalized medicine, cases like this one open new avenues for patients who were not responsive to traditional therapies, potentially transforming the management of previously intractable cancers. DOI - https://doi.org/10.18632/oncotarget.28659 Correspondence to - Andrew Hendifar - andrew.hendifar@cshs.org Video short - https://www.youtube.com/watch?v=VnfohGvfMoM Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28659 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, pancreatic cancer, immunotherapy, metastasis 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

In today's episode, we had the pleasure of speaking with David R. Gandara, MD, about biomarker testing in lung cancer. Dr Gandara is the chief medical officer of the International Society of Liquid Biopsy, the co-director of the Center for Experimental Therapeutics in Cancer, and the senior advisor to the director at the University of California Davis Comprehensive Cancer Center in Sacramento, and an adjunct clinical professor in the Translational and Clinical Research Program at the University of Hawaii Cancer Center in Honolulu.  In our exclusive interview, Dr Gandara discussed the optimal use of liquid biopsy for patients with non–small cell lung cancer (NSCLC), the ins and outs of testing for KRAS mutations, and available treatment options for patients with KRAS-mutant NSCLC.

We love to hear from our listeners. Send us a message. This week, it's another “Business of Biotech-meets-Business-of-RNA” takeover with Circio CEO Erik Digman Wiklund, Ph.D. and guest co-host Anna Rose Welch of Advancing RNA.  While Circio's legacy is in cancer immunology (it still boasts a cancer vaccine candidate targeting KRAS driver mutations), the company made a bold pivot, of sorts, when it committed headlong to the circular RNA future. Now, it's in the throes of fine-tuning a platform for the development of novel circRNA medicines for rare disease, vaccines, and cancer. On this episode of the Business of Biotech, we go deep inside the story behind the pivot, we explore the RNA therapeutic platform-versus-product appetite among biotech investors, and Dr. Digman Wiklund shares insights into the challenges his company overcame to enable such a dramatic shift in focus. Access this and hundreds of episodes of the Business of Biotech videocast under the Listen & Watch tab at bioprocessonline.com. Subscribe to our monthly Business of Biotech newsletter. Get in touch with guest and topic suggestions: matt.pillar@lifescienceconnect.comFind Matt Pillar on LinkedIn: https://www.linkedin.com/in/matthewpillar/