Podcasts about cfdna

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

Imagine if a single blood test could tell clinicians in real time how successful a cancer surgery has been. A recent study from the University of Brasília, published in Oncotarget, suggests that such an approach might soon be possible. By tracking changes in cell-free DNA (cfDNA) levels before, during, and after colorectal cancer (CRC) surgery, researchers have found a potential new way to monitor tumor removal and predict patient outcomes. Cell-Free DNA and Colorectal Cancer Surgery Cell-free DNA consists of tiny fragments of genetic material that are released into the bloodstream when cells break down. In healthy individuals, these fragments come from normal cell turnover, but in cancer patients, some of this DNA originates from tumor cells. cfDNA detection has been used to track cancer progression and treatment response in diseases like lung, breast, and CRC. What had not been investigated until now was how cfDNA levels fluctuate during cancer surgery itself. Since surgery is the primary treatment for CRC, understanding how cfDNA levels change during surgical intervention could provide valuable insights into whether the tumor has been fully removed and how the patient's body reacts to the procedure. The Study: Measuring Cell-Free DNA in Real-Time In the study, titled “Assessment of cfDNA release dynamics during colorectal cancer surgery,” led by first author Mailson Alves Lopes and corresponding author Fabio Pittella-Silva, scientists analyzed ​​blood plasma samples from 30 CRC patients at three critical time points—before, during, and after surgery. Using highly sensitive genetic tests, they measured changes in cfDNA concentration to determine whether surgery had a direct impact on its release. The goal was to check whether cfDNA could serve as a biomarker for evaluating surgical effectiveness and predicting the probability of cancer recurrence. Full blog - https://www.oncotarget.org/2025/02/26/how-a-simple-blood-test-could-predict-colorectal-cancer-surgery-success/ Paper DOI - https://doi.org/10.18632/oncotarget.28681 Correspondence to - Fabio Pittella-Silva - pittella@unb.br Video short - https://www.youtube.com/watch?v=jC5_xqIrbtA Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28681 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, colorectal cancer, cfDNA, surgery 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

Join us as we review recent articles and news featured in The DIGEST issues #59-61, including cfDNA and incidental detection of cancer in pregnancy, vitamin K2 for nocturnal leg cramps, the danger of as-needed anti-hypertensive medications in the hospital, GLP-1 agonists for alcohol use disorder, short-course (7 vs 14 days) antibiotics for bacteremia, and patient-collected HPV testing for cervical cancer screening. Fill your brain hole with a fully digestible meal! Featuring Laura Glick MD, Nora Taranto (@norataranto), Paul Williams (@paulnwilliamz), and Matt Watto (@doctorwatto).  Claim CME for this episode at curbsiders.vcuhealth.org! Patreon | Episodes | Subscribe | Spotify | YouTube | Newsletter | Contact | Swag! | CME Show Segments 00:00 Introduction and Overview 02:57 The IDENTIFY study: Non-Invasive Prenatal Testing and Cancer Detection with cfDNA 05:54 Implications of Non-Reportable Results in Prenatal Testing 08:51 Vitamin K2: A New Approach to Managing Nocturnal Leg Cramps 12:07 Practicality and Future of Vitamin K2 in Clinical Practice 23:21 The Dangers of As-Needed Antihypertensives in the hospital 32:21 Exploring GLP-1 Agonists for Alcohol Use Disorder 40:24 Shorter Antibiotic Courses in Sepsis 46:09 Advancements in Patient-Collected HPV Screening for cervical cancer Credits Written and Produced by: Nora Taranto MD, Laura Glick MD, Matthew Watto MD, FACP; Paul Williams MD, FACP Show Notes: Nora Taranto MD Cover Art: Matthew Watto MD, FACP Hosts: Nora Taranto MD, Laura Glick MD, Matthew Watto MD, FACP; Paul Williams MD, FACP    Reviewer: Emi Okamoto MD Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP Technical Production: PodPaste Disclosures The Curbsiders report no relevant financial disclosures.  Sponsor: Bombas Head over to Bombas.com/curb and use code curb for 20% off your first purchase. Sponsor: Pretty Litter  Go to PrettyLitter.com/curb to save twenty percent on your FIRST order and get a free cat toy.  Sponsor: Rocket Money  Cancel your unwanted subscriptions and reach your financial goals faster with Rocket Money. Go to RocketMoney.com/CURB today.

BUFFALO, NY - January 27, 2025 – A new #research paper was #published in Oncotarget's Volume 16 on January 21, 2025, titled “Assessment of cfDNA release dynamics during colorectal cancer surgery." Researchers from the University of Brasília investigated how cell-free DNA (cfDNA) levels in the blood change before, during, and after colorectal cancer surgery. The study found that cfDNA levels increase significantly during and after surgery. The findings suggest that cfDNA could help clinicians evaluate surgery effectiveness and monitor patient outcomes. cfDNA consists of small DNA fragments released into the bloodstream when cells die and break apart. In healthy individuals, cfDNA usually comes from normal cell turnover, while in cancer patients, some of it originates from tumor cells. Measuring cfDNA levels offers valuable insights into a patient's condition and is already being used to track disease progression and treatment response in cancers such as lung, breast, and colorectal cancer. Colorectal cancer is one of the most common cancers worldwide, affecting millions of people each year. Surgery is often the primary treatment, but up to 50% of patients experience cancer recurrence afterward. In this study, the research team, led by first author Mailson Alves Lopes and corresponding author Fabio Pittella-Silva, analyzed blood samples from 30 patients at three key time points: before, during, and after surgery. It was found that cfDNA levels increased nearly threefold during surgery and doubled after surgery compared to pre-surgery levels. The increases were even higher in individuals over 60, those with preexisting conditions such as diabetes or heart disease, and patients with elevated levels of carcinoembryonic antigen (CEA), a common cancer marker. Patients with the highest cfDNA levels were those with larger or more aggressive tumors, likely due to greater tissue damage during surgery. Additionally, longer surgeries were linked to higher cfDNA levels. “[...]we observed that cfDNA concentration may rise in correlation with the duration of the surgery, highlighting its potential as a marker of surgical quality.” These findings suggest that cfDNA could be a valuable, non-invasive biomarker for clinicians to monitor colorectal cancer patients. Tracking cfDNA levels may help better evaluate surgical outcomes and determine whether patients require closer follow-up care. While these findings are promising, further research is needed to standardize cfDNA testing and validate its usefulness. Larger studies could help establish cfDNA testing as a reliable tool for cancer care and postoperative monitoring, with the potential to become a routine part of clinical practice in the future. DOI - https://doi.org/10.18632/oncotarget.28681 Correspondence to - Fabio Pittella-Silva - pittella@unb.br Video short - https://www.youtube.com/watch?v=jC5_xqIrbtA 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

Dr. Rajesh Rao speaks with Dr. Jasmine H. Francis on whether sequencing of plasma-derived ctDNA can noninvasively diagnose ocular-involving histiocytosis. From her Ophthalmology Science article, “Plasma-Derived Cell-Free DNA for the Diagnosis of Ocular-Involving Histiocytosis.” Plasma-Derived Cell-Free DNA for the Diagnosis of Ocular-Involving Histiocytosis. Francis, Jasmine H. et al. Ophthalmology Science, Volume 4, Issue 5.

In this inaugural episode of the Surgical Oncology Insight series of SurgOnc Today®, Dr. Shishir Maithel, Editor of Surgical Oncology Insight, SSO's open-access journal, discusses with Dr. Brett Ecker the results of a systematic review and meta-analysis characterizing the incidence of cfDNA-positivity after resection of colorectal cancer liver metastases  with quantification of its sensitivity and specificity for postoperative recurrence, as reported in his article, "The Prognostic Role of Post-operative cfDNA after Resection of Colorectal Liver Metastases: A Systematic Review and Meta-Analysis."

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.CVS is laying off 2,900 employees as part of a cost-cutting plan and potential business breakup. Humana's Medicare Advantage star ratings have dropped significantly, impacting profits. Healthcare workers face burnout, while the payer-provider relationship is evolving. Mission Hospital in North Carolina is struggling after Hurricane Helene, and Steward CEO Ralph de la Torre is being sued by senators. Healthcare companies are urged to prioritize patient-centric experiences. The text also highlights upcoming healthcare conferences, telehealth trends, and insights into the relationship between providers and payers.The FDA has officially declared the end of the shortage of Zepbound and Mounjaro, putting pressure on companies selling compounded alternatives. Biopharma conferences in 2025 are important for showcasing clinical trial results. The FDA is set to make several key decisions in the fourth quarter, including approving a rival to a popular Pfizer heart drug. Roche plans to address an $8 billion sales gap due to biosimilar competition. Lilly is investing $4.5 billion in a "foundry" for advanced drug manufacturing. Additionally, there are resources available on topics such as AI in clinical research, genetic screening, gene therapy, and biosimilars. Other industry news includes potential sales of pharma units by Chinese company Wuxi, and the US's commitment to African manufacturing in HIV programs.Sanofi has sold the global rights to a rare autoimmune drug for cold agglutinin disease to Recordati in a potential $1 billion deal. Recordati will make an upfront payment of $825 million to Sanofi, with milestone payments of up to $250 million. Meanwhile, Novo's lowest dose of Wegovy remains on the FDA's drug shortage list. AbbVie has trimmed its full-year earnings guidance due to R&D milestone costs, following the success of its Parkinson's disease candidate Tavapadon. Relay Therapeutics is laying off 10% of its workforce to streamline its research organization. The pharma industry is prioritizing scaling GLP-1 manufacturing capacity to meet the demand for weight loss drugs. Lilly has ended its obesity drug shortage, while Novo continues to face shortages. WBL's proprietary library prep for cfDNA whole genome sequencing aims to enhance specificity, sensitivity, and data quality at low concentrations. In other news, BMS has received FDA approval for an Opdivo regimen in NSCLC and Bavarian Nordic's MPox shot shows antibody responses wane after 6 to 12 months.Dr. Matthew Schrag, a vascular neurologist at Vanderbilt University, is not prescribing the new Alzheimer's disease treatments, Kisunla and Leqembi, due to concerns over risks and costs. Schrag has a history of challenging prevailing science in Alzheimer's and has exposed instances of potential misconduct by researchers. In 2021, he raised allegations of data manipulation against Cassava Sciences, leading to ongoing scrutiny and calls for their phase 3 trials to be stopped. Despite distancing himself from the controversy, Schrag's findings have had a significant impact on the company. The article also discusses Roivant's unique approach to drug development, the latest advances in oncology research, and the challenges in navigating the path from preclinical studies to regulatory approval for gene therapies. The text highlights the importance of efficient therapeutic development processes and increasing diversity in clinical trials. Additionally, it provides links to resources on selecting clinical trial sites, unlocking partnerships for small biotech firms, and optimizing AAV manufacturing processes. The newsletter also includes updates on Medicare drug price talks, a groundbreaking trial for lung cancer treatment, and a map of a fruit fly's brain that has impressed neuroscientists.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. Bayer has developed a successful audience targeting strategy that drives meaningful engagement, with Crossix audience segments optimizing campaigns and aligning messaging more closely with the patient journey. This precision targeting has proven effective in reaching the most qualified audience and increasing engagement.Philips issued a fix for ventilator problems linked to injuries and deaths, Siemens Healthineers received FDA approval for a 3D mammography system, and Synchron's brain-computer interface technology met safety goals. Additionally, the wearables market is expected to see growth, while the FDA missed a target date for releasing rules on pulse oximeters. Medtech Dive provides insights on medical technology trends and top conferences in 2025.A private equity firm, TPG, is set to acquire a majority stake in e-prescribing giant Surescripts. HCA's Mission Hospital in North Carolina faces challenges after Hurricane Helene, while UHS has been forced to pay significant damages related to child sexual abuse allegations. Efforts to combat burnout among healthcare workers are highlighted, along with sponsored content on safeguarding healthcare against cybercrime.Eli Lilly is investing $4.5 billion in a new manufacturing and research center in Indiana, while Amgen faces a class action lawsuit and Johnson & Johnson invests $2 billion in a North Carolina facility. Bayer, J&J, and Pfizer are collectively laying off nearly 500 employees, with new developments in cFDNA methylation assays and royalty financing for biopharma companies. ImmunityBio is also undergoing layoffs in California.Roche is facing an $8 billion sales gap due to biosimilar competition, prompting investments in new blockbuster drugs. Kailera Therapeutics has secured funding for obesity drugs, and the cell and gene therapy industry is experiencing rapid growth. Pharmavoice covers these topics and more in their daily newsletter.2seventy Bio is close to reaching cash flow breakeven, attributing their survival to transparency and a committed staff. Pfizer's withdrawal of sickle cell therapy Oxbryta has raised questions among investors. Royalty financing has become crucial for biopharma companies as traditional fundraising methods falter. Lilly's drug pricing practices are under scrutiny compared to Novo Nordisk. Various updates on investments, layoffs, and legal actions can be found on Biospace's website.

Our immediate past episode summarized a validation study of cell-free DNA (cfDNA) isolated from maternal plasma for fetal RBC genotyping in alloimmunized patients. And now, in this episode, we will highlight a BRAND NEW ACOG Clinical Practice Update on this very subject! YEP... we now have new ACOG guidance regarding using maternal derived cfDNA for fetal RBC antigen detection as an option for care in alloimmunized pregnancies. This is how "medicine moves fast"! Listen in for details.

In September 2022, a cell-free DNA assay using next-generation sequencing and quantitative counting tech for fetal antigen status determination became clinically available in the USA. This allowed maternal screening for fetal RBC genotypes for RH negative patients. This test was recognized by thre ACOG in March 2024 as one option to “triage” anti-D immunoglobulin in RH negative women. But can this technology be trusted in alloimmunized patients? In women with antibodies against foreign antibodies, this cell free DNA fetal screening option MUST get it right. We now have that data. In this episode, we will summarize remarkable results, published ahead of print on July 25, 2024 in the Green Journal. This study is a win for science and prenatal care. Listen in for details (BillontoOne, Inc is not a sponsor for this podcast).

Dr. Medhat Askar joins the podcast to discuss the utility and validation of donor-derived cell-free DNA (dd-cfDNA) testing for solid-organ recipients. Dr. Askar also discusses the regulatory status of dd-cfDNA in the United States.

Proving that our podcast tagline, “Medicine Moves Fast” is true… this episode highlights something that is, once again,

Organ transplantation is a modern marvel, with more than 157,000 solid organ, and more than 9,000 marrow and blood transplants occurring worldwide in 2022. Organ donor and recipient matching and compatibility screening has progressed significantly in recent decades as molecular methods have progressed rapidly to support this and other fields. Specifically, typing of human leukocyte antigens (HLAs) has expanded to consider ethnic population variation and cell free DNA (cfDNA) monitoring is now being used to monitor recipients for biomarkers that indicate organ rejection.  Our guest for this episode, Dr. Lee Ann Baxter-Lowe, Director of the HLA Laboratory at Children's Hospital Los Angeles has been working in the field of transplantation science for virtually her entire career. Join us for a great explanation of the science and a first-hand recounting of developing the assays, from decades ago, before thermal cyclers existed, to her cutting-edge work using digital PCR to progress the field even further. Lee Ann also shares very personal aspects of her career journey in her conversation with Cassie. This includes her describing the scientific “studies” of her and her cousin as children, her venturing into the world of HLA typing when it was emerging, and the role her family has played in her career, which gets personal quickly when she shares that her husband is currently dealing with a blood malignancy. Visit the Absolute Gene-ius page to learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Alex Aravanis is a leader in research and development of technologies and clinical tests utilizing the latest tools in DNA analysis and data science. In this episode, Alex delves into two interconnected topics: liquid biopsies and epigenetics. He begins by tracing the trajectory of genome sequencing and tumor sequencing, setting the stage for a detailed exploration of liquid biopsies as an early cancer detection method. The discussion encompasses key concepts such as cell-free DNA, DNA methylation, sensitivity, specificity, and the predictive values associated with liquid biopsies. Transitioning to epigenetics, Alex examines the intricate interplay of DNA methylation and aging biology and explores the possibility of using cellular reprogramming to reverse epigenetic changes that occur with aging. We discuss: Alex's background in applying engineering to problems in medicine [3:15]; A primer on human genetics, and the history and current landscape of DNA sequencing [11:00]; The advent and evolution of liquid biopsies for early detection of cancer [23:15]; The role of cell-free DNA in cancer detection: how incidental findings in non-invasive prenatal testing led to the development of liquid biopsies [40:15]; The development of a universal blood test for cancer detection and a discussion of specificity of tests [46:00]; Advancements in cell-free DNA analysis and development of a multi-cancer screening test at GRAIL [51:00]; DNA methylation explained [58:15]; Optimizing cancer detection with methylation analysis of cfDNA in small blood samples [1:02:45]; The importance of understanding sensitivity, specificity, positive predictive value, and negative predictive value in cancer screening [1:08:00]; The performance of the GRAIL Galleri test and its ability to detect various types and stages of cancer [1:21:00]; Do early cancer detection methods, like liquid biopsies, translate to improvement in overall survival? [1:27:45]; The role of epigenetics in aging [1:39:30]; How cell-free DNA methylation patterns can help identify a cancer's tissue of origin [1:45:30]; Cellular and epigenetic reprogramming and other exciting work in the field of aging [1:52:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

CME credits: 1.00 Valid until: 17-01-2025 Claim your CME credit at https://reachmd.com/programs/cme/testing-for-solid-tumors-tissue-and-liquid-biopsy-approaches-using-ngs-technologies-for-cfdna-and-ctdna-analysis/16555/ HER2-targeted treatments have been extensively researched and approved in breast, gastric, and non-small cell lung cancers. Are these same therapies effective at treating other HER2-positive tumors? Join our faculty as they examine the potential role for HER2-directed antibody-drug conjugates in treating advanced solid tumors and discuss the latest data around the efficacy and safety of these agents.

Dr. Rachna Shroff, chair-elect of the 2023 ASCO GI Cancers Symposium, and guest host Dr. Shaalan Beg discuss new research presented at GI23, including new data from SWOG 1815 in biliary tract cancers, advances in biomarker studies in mCRC such as the PARADIGM trial, and promising updates in ctDNA technology. She also highlights the exciting potential of AI in oncology. TRANSCRIPT Dr. Shaalan Beg:  Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of Oncology at Science 37. Today we'll be discussing key abstracts and other highlights from the 2023 ASCO Gastrointestinal Cancer Symposium, which celebrated 20 years of transformative care in GI cancers. I'm delighted to welcome Dr. Rachna Shroff, the chair-elect of this milestone meeting. Dr. Shroff is the interim division chief of Hematology Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for Clinical and Translational Research and is the chief of GI Medical Oncology. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Shroff, it's great to have you back on the ASCO Daily News podcast. Dr. Rachna Shroff: Thank you so much for having me. I'm so excited to be here. Dr. Shaalan Beg: The ASCO GI Cancers Symposium has been heralded as one of the biggest conferences in the GI cancer space and has occupied this space for the past two decades. Some would say that this year's conference was probably the best GI Cancers Symposium to date. Can you comment on the 20th anniversary milestone and the impact of the symposium on GI cancers? Dr. Rachna Shroff: Absolutely, and that's so great to hear that that's the feedback that you've heard. I have to say GI ASCO is absolutely my favorite meeting of the year, so that is my full disclosure. But I think that this was a tremendous meeting, and I think it was so beautiful that it was also coinciding with the 20th anniversary. It meant so much to us to have Dr. Margaret Tempero open the meeting because she really was the impetus for creating a GI cancer-focused meeting that really brought together multidisciplinary expertise. And so to us, that is what this 20th anniversary represented—20 years of multiple different specialties coming together to discuss how to improve cancer care for patients with gastrointestinal malignancies. And it has been a transformative meeting to see the impact of research presented at this meeting and how it has been implemented over the course of 20 years. And I completely agree that this year in and of itself had some incredible pivotal data that there is no doubt will be practice-changing, and that is absolutely the purpose. I also think that the beauty of this meeting is the networking opportunities for all of us to come out of our individual silos, come together, and discuss cross-cutting care across the spectrum of GI malignancies. And I think that this meeting really did that quite well. Dr. Shaalan Beg: There were many practice-changing studies that made headlines this year, and for me, one of the most anticipated studies was a trial that you led for cholangiocarcinoma and much-anticipated results. The study finished enrollment at a record pace. Can you share your key findings of cholangiocarcinoma? And I'd really like to hear your perspective on cholangiocarcinoma studies. Dr. Rachna Shroff: Yes, it was actually a really big year in the hepatobiliary space, and I was proud to present SWOG 1815, LBA 490, which was the pivotal randomized phase 3 trial looking at gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin. This was a study that was opened across the entire NCTN and based on a single-arm phase 2 trial that had shown some promising early efficacy of the triplet chemotherapy regimen. As you mentioned, this study accrued 441 patients in two years. And it's really a testament to the fact that the cooperative group mechanism can and should be asking important questions in large, randomized studies and that it is even possible to do in what are historically thought of as, quote-unquote, “rare tumors.” The study was a randomization of two to one to the triplet chemotherapy versus the standard of care for newly diagnosed biliary tract cancer patients. And the primary endpoint was median overall survival. And while the median OS of the triplet regimen was numerically improved at 14 months compared to 12.7 months, this did not meet statistical significance. Other efficacy endpoints, including median progression-free survival and overall response rate, were also numerically improved but not statistically significant, with an overall response rate of 31% with the triplet regimen versus 22%. There were some prespecified stratification factors, including disease site and disease stage, and there may be some interesting signals that bear out of that in terms of perhaps gallbladder cancer and locally advanced patients may be benefiting from the triplet regimen a little bit more, but these are small numbers, and we would really need to explore that in a more rigorous prospective manner. The toxicities were, not surprisingly, there, especially hematologic toxicities. I will say for those of us that use this regimen in practice, we use it a little bit differently than what was done in SWOG 1815, but you can't deny that there were significantly higher grade 3-5 toxicities with anemia neutropenia and thrombocytopenia, though the treatment discontinuation rate did not differ. I think the next steps are really going to be the ongoing biomarker analyses. The study had archival tissue and prospective blood collection and we know that in the space of cholangiocarcinomas and biliary cancers, molecular complexities absolutely play a role in how patients do and how they respond to therapies. So that's going to be an important next step, I think, for this study. Dr. Shaalan Beg: Speaking of biomarkers and an impact on GI cancers, the other malignancy where biomarkers are having a much greater impact than other GI cancers is colon cancer. Another year where we continue to see advances in our understanding of molecularly targeted treatments for colon cancer. What caught your eye? Dr. Rachna Shroff: Well, there were a lot of really interesting studies happening in this space and as a biliary person, one of the first things I got excited about was seeing Abstract 139 that looked at pemigatinib, which is the drug we are very familiar with in cholangiocarcinoma. This was a single-arm phase two study looking at the use of the FGFR inhibitor pemigatinib in metastatic colorectal cancer patients who had FGFR alterations. And so this was a study that was opened through the ACCRU mechanism. It was multicenter with assignment two-stage design and it was specifically for patients with FGF and FGFR-altered metastatic colorectal cancer who had progressed on standard therapies. There was a prespecified interim analysis for futility after 12 evaluable patients and so 14 patients were enrolled in the first stage of the study and evaluated for the primary endpoint of objective response. What was seen and the study was subsequently stopped is that there was really not much efficacy, there was no evidence of safety signals, but this did not seem to be a very active drug in patients with FGFR alterations with no objective response noted. So, the study was stopped with the recognition that perhaps the FGFR translocation or fusion patient population may be something to explore since they did not look at that in this study. The other kind of study that I think is really important was important work of Dr. Raghav and colleagues through SWOG. This was SWOG 1613 Abstract 140. This was the first real study that was investigating targeting HER-2 overexpressed and amplified metastatic colorectal cancer who had RAS wild-type tumors. And it was based on, obviously, some early signals of the effectiveness of HER-2 targeting in metastatic colorectal cancer. And this was a large study looking at pertuzumab and trastuzumab in these patients. They were compared to cetuximab and irinotecan, and the initial plan was for a much larger study. Unfortunately, accrual was really slow so the study was really kind of reformatted and a total of 54 patients were randomized, 26 to the trastuzumab arm and 28 to the CetIri or cetuximab and irinotecan arm. What was seen was that you can absolutely use HER-2 targeting therapies with trastuzumab and pertuzumab in these patients. It was safe and there were some obvious signs of efficacy in terms of overall response rate with an overall response rate of 31% compared to the CetIri arm. Crossover was allowed from the CetIri arm to trastuzumab and pertuzumab. So just that's important to keep in mind when they start to follow out the survival data. But unfortunately, because this study did not accrue, it was stopped early and it's really hard to understand in terms of power calculations the impact of trastuzumab pertuzumab. Of course, we can't talk about this without recognizing that the FDA approval based on the MOUNTAINEER study for tucatinib and trastuzumab came through during GI ASCO. So clearly HER-2 targeting is here to stay in colorectal cancer. Dr. Shaalan Beg: So technology is advancing every year and it's important that we are aware of these advances and how they impact our patients. Probably one of the most exciting technologies in oncology in general is the evolution of ctDNA. And it's been amazing to watch that field unfold as we understand how to use circulating biomarkers for early detection of cancer, for minimal residual disease detection, even as a biomarker of response. What caught your eye when it comes to the use of ctDNA in GI cancers, and how do you see this space develop in the next couple of years? Dr. Rachna Shroff: I completely agree. I think the technology of ctDNA is so incredibly exciting and as somebody who does not actively see and treat colorectal cancer, I'm a little bit envious of my colleagues in that space because the strides that have been made in terms of understanding the utility of ctDNA, especially in colorectal cancer, has just been tremendous and even for the last two to three years. One perfect example of integrating that sort of technology into treatment paradigms is the PARADIGM trial, Abstract 11, which was looking at the concept of hyperselection of patients with RAS wild-type metastatic colorectal cancer who were on the PARADIGM trial which basically looked at frontline FOLFOX with panitumumab versus bevacizumab in patients with RAS wild type left-sided metastatic colorectal cancer. So, you know, the initial data from PARADIGM had demonstrated a longer median overall survival 37.9 months versus 34.3 months, but very smartly, the investigators had also collected baseline plasma ctDNA in the biomarker component of this study and used a custom panel that looked at gene alterations for hyperselection and that included KRAS, NRAS, PTEN, and extracellular domain EGFR mutations HER-2 and MET amplifications, as well as some fusions like ALK, RET, and NTRK. And so out of the 802 patients in the full set, 91% - 733 patients - actually had pretreatment samples for ctDNA, which is really in and of itself, I think, tremendous. And when you break it down, about 28% had at least one gene alteration, and that was across each of those different genes that they were looking at. In the 72% of patients who were defined as hyperselected without any gene alterations, the OS was actually longer with panitumumab versus bev, and that actually was independent of sidedness with hazard ratios that kind of ranged from 0.76 to 0.82. And OS was similar or inferior with panitumumab versus bevacizumab again, regardless of sidedness in patients with any of these gene alterations. And so I think it's a really interesting concept that you can use ctDNA to define negative hyperselection rather than looking at left sided and right sided to really help select patients with frontline therapy in terms of using panitumumab versus bevacizumab. And with the speed with which ctDNA can be obtained, this actually seems like something that could be implemented into clinical practice, which is, I think, really the important component of that. There were a number of other really interesting abstracts. Abstract 5, presented by Dr. Cohen and colleagues, really looked at the kinetics of circulating cell-free DNA and how that kind of relates to minimal residual disease detection rates. And this was in patients with resected stages one through three colorectal cancer. And so, this was a retrospective study, so we have to keep that in mind. And it was multi-institutional in really over 16,000 patients with stages 1 through 3 colorectal cancer. But the complete dataset had about 417 patients and basically the patients' circulating cell-free DNA levels, the total cfDNA, were compared to the ctDNA MRD positivity rates and they looked at very specific time points after surgery. What the authors generally found was that the postoperative cfDNA correlated well with ctDNA positivity and that there was really the ability to see plasma cfDNA levels kind of track and follow with the very specific MRD windows that were being looked at, which really, again, just kind of talks about leveraging this technology in terms of real-world and real-time application and better understanding and informing us of minimal residual disease post what is thought to be curative resection. The last one that I thought was really interesting in relation to ctDNA was actually looking at anal cancer and following ctDNA in patients who were treated with definitive chemoradiation. This was a study that was looking at 31 patients with anal squamous cell carcinoma who were treated with definitive chemo radiation and underwent ctDNA response. The majority of these patients had stage 3 disease and the majority of them received the standard 5-FU Mitomycin with radiation. The patients had ctDNA testing performed in 25 of these patients at baseline and then a smaller number over the course of time, some during chemoradiation. And then they looked again at 30 days post chemoradiation. And at baseline, 88% of patients had detectable ctDNA with those with stage three disease having numerically higher baseline ctDNA levels. And basically what they found was that over the course of treatment, ctDNA levels decreased among the patients with detectable ctDNA. And then ctDNA that tested during chemo radiation showed a drop in decline and were going into molecular remission at a time point in which it was subsequently confirmed that they had a clinical complete response. So, the suggestion here is that the time to molecular ctDNA remission was significantly shorter than being able to see that clinical complete response, which suggests that using surveillance ctDNA monitoring could be an earlier response assessment for patients with anal squamous cell carcinoma who are undergoing definitive therapy. Now, obviously this needs to be confirmed in a larger manner, but again, really suggests that we could be understanding how we're doing with treatment in more of a real-time fashion, which I just think is incredible for those of us who are making sure that we are doing and taking the right approaches for these patients. Dr. Shaalan Beg: One of the major transformative announcements that took place only a couple of months before the GI Cancer Symposium was the announcement of ChatGPT. And we heard a lot of discussion on how it can be used for improving cancer care, improving drug development, and in general, artificial intelligence and machine learning. We've been hearing these buzzwords for such a long time, to the point that a lot of people are probably just filtering it out and then this tool comes up and it makes it real. And we're seeing different people apply these technologies in different ways. But there is tremendous potential in how this technology can improve clinical trials, drug development, and early diagnosis. And luckily, we had already secured a keynote speaker, Dr. Matthew Lundgren from Nuance Communications, and he was invited to talk about artificial intelligence, machine learning, and how it applies to cancer care. I'm really curious to hear what your highlights were from his address and how you see this impacting your day-to-day, or just the ecosystem of which we're all part of. Dr. Rachna Shroff: Yeah, I will say that his keynote was really one of the highlights of the entire meeting for me. And that is coming from somebody who doesn't really know– I know who I'm speaking to, but somebody who does not truly understand the way AI is moving. And so, I was joking with him that it was like AI 101. And I really, really appreciated the way he was able to kind of speak to a crowd that he doesn't normally speak to and help us really understand the way in which artificial intelligence can be integrated into healthcare, and specifically oncology. To me, I think what were the most salient takeaways from his address was really about how this is just a rapidly evolving field and we need to be a little bit ahead of the eight ball when it comes to thinking how we can smartly leverage artificial intelligence like you mentioned, to improve our clinical research efforts, to improve access, and to improve fully integrating AI into our EMR, so that we can really leverage that technology and ensure that we are capturing every potential patient for a clinical trial and be smarter about how we're even approaching things. I mean, I loved him talking about the prior authorizations and that sort of thing, and the ways in which we can decrease the burden on health care providers and really let us focus on the areas that we need to focus on. The one thing that I thought was a really important point, though, and I think a number of people asked him, was about how using this technology has the potential to create more gaps and disparities and how can we be smart to ensure that we don't broaden those gaps. And I think that is a really important point that we all need to think about because we know that especially when we think through clinical trials, there's already underrepresentation of certain populations and certain geographic regions. And so, I think that was a really important takeaway for me is how can we make sure that we work and partner with those who are creating these technologies to ensure that we aren't taking two steps forward and four steps back. Dr. Shaalan Beg: It really calls into question how we define productivity and what our value in the entire delivery system really is. And I think from people who are in middle school or high school to people who are in college and even folks who are in the field as you and I are, it's forcing us to rethink what we bring to the table in a way that we've never been challenged to ask that question ever before. Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: So, thank you very much, Dr. Shroff. This was wonderful. Thank you for sharing your insights with us today. And we thank you and Dr. George Chang, the chair of the ASCO GI Cancers Symposium, and everyone who worked so hard to develop a robust program this year.  Dr. Rachna Shroff: Thank you. It was so wonderful to be able to speak about it. And thank you to all of the attendees for making it such a memorable meeting. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your 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, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn  Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics        

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.09.522931v1?rss=1 Authors: Ngo, A. T., Sarkar, A., Yarovoi, I., Levine, N., Bochenek, V., Zhao, G., Rauova, L., Kowalska, M. A., Eckart, K., Mangalmurti, N., Rux, A., Cines, D. B., Poncz, M., Gollomp, K. Abstract: Neutrophil extracellular traps (NETs) are abundant in sepsis, and proposed NET-directed therapies in sepsis prevent their formation or accelerate degradation. Yet NETs are important for microbial entrapment, as NET digestion liberates pathogens and NET degradation products (NDPs) that deleteriously promote thrombosis and endothelial cell injury. We proposed an alternative strategy of NET-stabilization with the chemokine, platelet factor 4 (PF4, CXCL4), which we have shown enhances NET-mediated microbial entrapment. We now show that NET compaction by PF4 reduces their thrombogenicity. In vitro, we quantified plasma thrombin and fibrin generation by intact or degraded NETs and cell-free (cf) DNA fragments, and found that digested NETs and short DNA fragments were more thrombogenic than intact NETs and high molecular weight genomic DNA, respectively. PF4 reduced the thrombogenicity of digested NETs and DNA by interfering, in part, with contact pathway activation. In endothelial cell culture studies, short DNA fragments promoted von Willebrand factor release and tissue factor expression via a toll-like receptor 9-dependent mechanism. PF4 blocked these effects. Cxcl4-/- mice infused with cfDNA exhibited higher plasma thrombin anti-thrombin (TAT) levels compared to wild-type controls. Following challenge with bacterial lipopolysaccharide, Cxcl4-/- mice had similar elevations in plasma TAT and cfDNA, effects prevented by PF4 infusion. Thus, NET-stabilization by PF4 prevents the release of short fragments of cfDNA, limiting the activation of the contact coagulation pathway and reducing endothelial injury. These results support our hypothesis that NET-stabilization reduces pathologic sequelae in sepsis, an observation of potential clinical benefit. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Raja Dandamudi summarizes the results of his study "Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney Transplantation," on behalf of his colleagues.

Let's talk about cfDNA and how a new test is soon to be coming to a PCP office near you to screen healthy patients for all cancers in a single blood test.

"There's an entire field of fragmentomics with a whole lot of people working on it. The DNA which is shed into the bloodstream has a certain length. The length of ctDNA is shorter than cfDNA, and depending on where the cancer cell is located, the fragment size and pattern is different. So you can actually deduce information about the tissue of origin from the fragment length and pattern. And that's just the beginning."

In this episode we discuss the new Jada postpartum hemorrhage device. More importantly, we discuss the process for choosing to utilize new interventions in clinical practice. Then we discuss a recent New York Times article detailing the problem of false positives in the noninvasive prenatal screening tests. 

In this episode, we are honored to have Sheetal Parmar, who is here to chat about genetic counseling, something new to many of us and something other people may have heard about. Sheetal is a board-certified genetic counselor and the vice president of medical affairs at Natera. Natera is a global leader in cell-free (cfDNA) testing focusing on women's health, oncology, and organ health. Sheetal shares with us that genetic counseling is the process of helping people understand and adapt to the medical, psychological, and family implications of genetic diseases and their contribution of genetic disease to their families. Also, what a genetic counselor is and how their skills are used across any medical field. She tells us how genetic counselors work throughout Natera in patient and health care provider management. Sheetal also dives deep into how beneficial genetic testing can be to understand one's health. This episode is incredibly insightful regarding the many benefits of genetic testing and genetic counselors, tune in and enjoy! Click this link to the show notes, transcript, and resources: outcomesrocket.health

Welcome to Season 3 of the Personalized Medicine Podcast! We hope you all head a good start in 2022 and are ready to dive deep into the world of personalized medicine with us again.In this first episode of Season 3, we address a very important and, frankly speaking, underappreciated topic of sepsis, commonly known as bacterial blood poisoning. Did you know that last year, sepsis killed more people than 5 most common types of cancer combined? For this episode, our host Oleksandr Yagensky sat down with the co-founder and CEO of Noscendo, Dr. Philip Stevens. Philip and his team are developing diagnostic workflows based on detection of bacterial and fungal cell-free DNA from blood to detect infections.Listen to this episode to learn more about: ◦ The founding story of Noscendo ◦ Building a successful diagnostics startup in Europe ◦ Generation of clinical evidence for early stage startups ◦ Misconceptions about sepsis and sepsis diagnostics ◦ How NGS can help detect sepsis early ◦ Role of DNA sequencing in determining antibiotic resistance ◦ Philip's advice to aspiring life science entrepreneursGet in touch with Philip: ◦ LinkedIn: https://www.linkedin.com/in/philip-stevens-4ab68213b/ ◦ Twitter: https://twitter.com/noscendo ◦ Web: https://noscendo.com/Make sure to download the full show notes with our guest's bio, links to their most notable work, and our recommendations for further reads on the topic of the episode at pmedcast.com

In this episode, we are privileged to feature the amazing Dr. Paul Billings. Paul is the Chief Medical Officer and Senior Vice president of Medical Affairs for Natera. Natera is a global leader in cell-free (cfDNA) testing with a focus on women's health, oncology, and organ health. The company is an expert at the process and measurement of cell-free DNA and at providing that in context with genetic information as well. Dr. Billings educates us on cell-free (cfDNA) testing. He discusses how his company develops millions of testing opportunities in genetics that have given them incredible expertise in measuring very small amounts of cell-free DNA. He shares how Natera has developed a series of products to cast light on things like the health of a fetus, recurrence of cancer, and health of an organ transplant. Dr.l also shares his hypothesis on how a drug post organ transplant is working through constant monitoring of cfDNA. He talks about the three indications Natera is working on, providing clear explanations of how they add enormous value to genetics and healthcare, and specific examples of how Natera works. There are so many things to learn from this insightful and exciting conversation with Paul, so please tune in! Click this link to the show notes, transcript, and resources: outcomesrocket.health

Imagine a liquid biopsy test whose results would allow physicians to evaluate chemotherapy for every patient in real time. Richard Brand, CFO of DiaCarta, Inc., a translational genomics and personalized diagnostics company, discusses a recent data publication in "Nature Scientific Reports" that validates their cell-free DNA biomarker detection pre-treatment (chemotherapy) can predict how much treatment a patient needs. Their QuantiDNA™ cfDNA test, studied in this paper, is used to quantify the total amount of cfDNA directly from a plasma sample while the patient is undergoing cancer therapy. #DiaCarta #LiquidBiopsyTest Richard Brand is the Chief Financial Officer at DiaCarta Inc., a company delivering precision diagnostics. In his previous role, he helped raise $86 million as CFO for a private diagnostics company, Laboratory for Advanced Medicine, Inc. Over 2 years, helped generate 2x return and best performing biotech IPO for most of 2017 as CFO. Managed one-third of an institutional investment fund's portfolio, helping it grow to $1 billion from $400 million. Managed Robertson Stephens's biotech private placement business to number two ranking. Richard holds a MBA from the University of Chicago and is a former Board member for the University's and Booth School's NYC Alumni Clubs.

The Oncology Journal Club - Delivering Oncology News DifferentlyThe Oncology Podcast, brought to you by Oncology News Australia, is proud to present Episode 34 in our series The Oncology Journal Club.This week we have another great episode for you in our usual format. Craig Underhill gets us started by talking us through primary tumour resection plus chemotherapy versus chemotherapy alone for metastatic colorectal cancer patients.Hans Prenen gets stuck into the use of tipifarnib in head and neck squamous cell carcinoma with HRAS mutations and Eva Segelov continues to guide us through what she calls a ‘manifesto for good study design' – a key paper from our friend Bishal Gyawali, addressing biases in study design that distort the appraisal of clinical benefit.Just a quick note – Eva started her analysis of this paper in last week's episode so I recommend listening to Episode 33 if you've not already. Today's quick bites are as diverse as ever covering estimates for cancer incidence and death to 2040, plasma cfDNA genotyping, the CROSS trial, targeting metabolism to enhance immunotherapy and an excellent paper by our friend Heidi Probst on the patient experience of radiotherapy for breast cancer. If you're not familiar with Heidi check out Episode 32 ‘When the Oncologist gets cancer'.With the usual top quality banter, papers you won't hear of anywhere else and expert analysis from our Hosts, you are in for another great episode of The Oncology Journal Club!Full bios and the list of all papers discussed are available on our website.For the latest oncology news visit www.oncologynews.com.au and for regular oncology updates for healthcare professionals, subscribe for free to get the weekly The Oncology Newsletter.The Oncology Podcast - An Australian Oncology Perspective

Go online to PeerView.com/KXM860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this case-based activity, experts in oncology and primary care examine how to best integrate future blood-based cancer screening tools into clinical practice in order to reduce cancer-related morbidity and mortality. Upon completion of this activity, participants should be better able to: Explain the scientific principles behind cfDNA-based liquid biopsy as a tool for early cancer screening, including the strengths and limitations of liquid biopsy compared with those of conventional screening methods, Identify the diagnostic/screening role of novel cfDNA-based screening assays for early cancer detection in the primary care setting, Adapt current cancer screening protocols based on recent evidence on emerging cfDNA-based multicancer screening assays in order to improve sensitivity, specificity, and tumor localization accuracy, Employ patient-centered strategies to integrate novel cancer screening methodologies in the primary care setting, including as part of educational and screening protocols.

Go online to PeerView.com/KXM860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this case-based activity, experts in oncology and primary care examine how to best integrate future blood-based cancer screening tools into clinical practice in order to reduce cancer-related morbidity and mortality. Upon completion of this activity, participants should be better able to: Explain the scientific principles behind cfDNA-based liquid biopsy as a tool for early cancer screening, including the strengths and limitations of liquid biopsy compared with those of conventional screening methods, Identify the diagnostic/screening role of novel cfDNA-based screening assays for early cancer detection in the primary care setting, Adapt current cancer screening protocols based on recent evidence on emerging cfDNA-based multicancer screening assays in order to improve sensitivity, specificity, and tumor localization accuracy, Employ patient-centered strategies to integrate novel cancer screening methodologies in the primary care setting, including as part of educational and screening protocols.

Go online to PeerView.com/KXM860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this case-based activity, experts in oncology and primary care examine how to best integrate future blood-based cancer screening tools into clinical practice in order to reduce cancer-related morbidity and mortality. Upon completion of this activity, participants should be better able to: Explain the scientific principles behind cfDNA-based liquid biopsy as a tool for early cancer screening, including the strengths and limitations of liquid biopsy compared with those of conventional screening methods, Identify the diagnostic/screening role of novel cfDNA-based screening assays for early cancer detection in the primary care setting, Adapt current cancer screening protocols based on recent evidence on emerging cfDNA-based multicancer screening assays in order to improve sensitivity, specificity, and tumor localization accuracy, Employ patient-centered strategies to integrate novel cancer screening methodologies in the primary care setting, including as part of educational and screening protocols.

Go online to PeerView.com/KXM860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this case-based activity, experts in oncology and primary care examine how to best integrate future blood-based cancer screening tools into clinical practice in order to reduce cancer-related morbidity and mortality. Upon completion of this activity, participants should be better able to: Explain the scientific principles behind cfDNA-based liquid biopsy as a tool for early cancer screening, including the strengths and limitations of liquid biopsy compared with those of conventional screening methods, Identify the diagnostic/screening role of novel cfDNA-based screening assays for early cancer detection in the primary care setting, Adapt current cancer screening protocols based on recent evidence on emerging cfDNA-based multicancer screening assays in order to improve sensitivity, specificity, and tumor localization accuracy, Employ patient-centered strategies to integrate novel cancer screening methodologies in the primary care setting, including as part of educational and screening protocols.

Go online to PeerView.com/KXM860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this case-based activity, experts in oncology and primary care examine how to best integrate future blood-based cancer screening tools into clinical practice in order to reduce cancer-related morbidity and mortality. Upon completion of this activity, participants should be better able to: Explain the scientific principles behind cfDNA-based liquid biopsy as a tool for early cancer screening, including the strengths and limitations of liquid biopsy compared with those of conventional screening methods, Identify the diagnostic/screening role of novel cfDNA-based screening assays for early cancer detection in the primary care setting, Adapt current cancer screening protocols based on recent evidence on emerging cfDNA-based multicancer screening assays in order to improve sensitivity, specificity, and tumor localization accuracy, Employ patient-centered strategies to integrate novel cancer screening methodologies in the primary care setting, including as part of educational and screening protocols.

Go online to PeerView.com/KXM860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this case-based activity, experts in oncology and primary care examine how to best integrate future blood-based cancer screening tools into clinical practice in order to reduce cancer-related morbidity and mortality. Upon completion of this activity, participants should be better able to: Explain the scientific principles behind cfDNA-based liquid biopsy as a tool for early cancer screening, including the strengths and limitations of liquid biopsy compared with those of conventional screening methods, Identify the diagnostic/screening role of novel cfDNA-based screening assays for early cancer detection in the primary care setting, Adapt current cancer screening protocols based on recent evidence on emerging cfDNA-based multicancer screening assays in order to improve sensitivity, specificity, and tumor localization accuracy, Employ patient-centered strategies to integrate novel cancer screening methodologies in the primary care setting, including as part of educational and screening protocols.

FDA 批准降钙素基因相关肽单抗用于预防偏头痛和丛集性头痛的发作JAMA Neurology 妊娠与临床孤立综合征发病的关系J Am Coll Cardiol 复杂的颈动脉斑块是引起隐源性卒中的一个原因Nature子刊 颅内恶性肿瘤的无创检测Nature子刊 合成纳米颗粒治疗胶质母细胞瘤加那珠单抗（galcanezumab）降钙素基因相关肽（CGRP）受体位于疼痛信号通路、颅内动脉和肥大细胞中，其活化被认为在偏头痛的病理生理学中起着因果作用。加那珠单抗（galcanezumab）是一种CGRP单克隆抗体。和此前在《神经科星期四 Episode 4》中介绍的治疗急性偏头痛的CGRP受体拮抗剂包括：瑞美吉泮（rimegepant）和乌布吉泮（ubrogepant）；以及《神经科星期四 Episode 14》中介绍的预防偏头痛发作的依替尼单抗（eptinezumab）属于一类药物。2018年9月，FDA批准加那珠单抗用于预防偏头痛发作；2019年6月，FDA批准加那珠单抗用于预防丛集性头痛发作。《CONQUER研究：加那珠单抗预防偏头痛的安全性和有效性的3b期临床研究》Lancet Neurology，2020年10月 (1)这项多中心、随机、双盲、安慰剂对照的3b期研究，纳入2到4类偏头痛预防药物无效的患者655例，患者年龄在18-75岁之间，有发作性或慢性偏头痛，在50岁之前发生偏头痛，入组后随机接受安慰剂或加那珠单抗（120mg q1m * 3m）。在1-3个月期间，加那珠单抗治疗的患者偏头痛发作天数比安慰剂显著减少。与基线相比，加那珠单抗组每月平均少4·1天，而安慰剂组每月平均少1·0天（p < 0·0001）。加那珠单抗和安慰剂之间治疗紧急不良事件的类型和数量相似。结论：加那珠单抗在偏头痛的预防治疗方面优于安慰剂，并且在以前的多个标准预防治疗失败的患者中有良好的耐受性。 《加那珠单抗预防发作性丛集性头痛的临床研究》New England Journal of Medicine，2019年7月(2)阵发性丛集性头痛是一种神经功能障碍，其特征是每天头痛发作，持续数周或数月。共招募患者106人，随机分配接受加那珠单抗（300mg）或安慰剂组。基线期每周丛集性头痛的平均发作次数，加那珠单抗组为17.8，安慰剂组为17.3。在第1至3周中，加那珠单抗组每周平均减少为8.7次，而安慰剂组为5.2次（P =0.04）。在第3周，头痛频率降低≥50%的患者，加那珠单抗组为71%，安慰剂组为53%。除了加那珠单抗组8%的患者有注射部位疼痛外，不良事件发生率在组间没有实质性差异。结论：与安慰剂相比，在首次注射后的1-3周内，加那珠单抗300mg ip降低了偶发性丛集性头痛的发作频率。多发性硬化多发性硬化（multiple sclerosis，MS）是以中枢神经系统白质炎性脱髓鞘病变为主要特点的自身免疫病。本病最常累及的部位为脑室周围白质、视神经、脊髓、脑干和小脑，主要临床特点为中枢神经系统白质散在分布的多病灶与病程中呈现的缓解复发，症状和体征的空间多发性和病程的时间多发性。 多发性硬化症主要的模式和病程可以分为以下几种临床亚型：临床孤立综合征（CIS）、复发缓解型（RR）、继发进展型（SP）、和原发进展型（PP）。 《前瞻性队列研究：妊娠与临床孤立综合征发病的关系》JAMA Neurology，2020年12月 (3)多发性硬化症常诊断于育龄妇女，但妊娠是否能延迟脱髓鞘或临床孤立综合征（CIS）的首次发作尚无共识。研究的目的是探讨妊娠与CIS发病时间的关系。这个国际、多中心、前瞻性研究纳入2557名女性，CIS发病的平均年龄为31岁，发病前46%至少有1次怀孕，43%至少有1次分娩。首次怀孕的平均年龄为23.3岁，首次分娩的平均年龄为23.8岁。与从未怀孕过的女性相比，有过怀孕和分娩经历的女性发生CIS的时间较晚，延迟3.3年（P < 0.001）。与从未分娩过的女性相比，分娩过的女性发病年龄也较晚，延迟3.4年（P < 0.001）。孕产次数与发病延迟无关。结论：发病前怀孕和分娩与CIS发病时间之间存在关联，但与次数无关。需要进一步的研究来帮助解释怀孕和多发性硬化症发病之间关联的机制。《前瞻性观察性队列研究：持续免疫治疗与活动性继发进展性多发性硬化症患者残疾结果的相关性》JAMA Neurology，2020年11月 (4)研究旨在评价继发进展性多发性硬化的患者中残疾累计发生率，及是否能够通过治疗延缓残疾累积的进展。这项观察性队列研究中， 招募53680例多发性硬化的患者，其中4997例继发进展型，在1621例符合纳入条件的患者中，女性患者68.0%，发病时的平均年龄为33.9岁。共有661例（40.8%）患者在继发进展性多发性硬化期间经历了叠加性复发。早期治疗方案和残疾累计发生无关。继发进展期的高复发率与轮椅依赖的残疾风险增加有关（P = 0.009）。在继发进展性多发性硬化期间经历反复复发的患者中，抑制疾病进展的治疗与残疾进展率的降低和轮椅依赖风险的降低显著相关。结论： 继发进展型多发性硬化症患者中，残疾进展率与早期病程和治疗方案无关，但是与疾病复发相关。多发性硬化的治疗多发性硬化治疗的主要目的是抑制炎性脱髓鞘病变进展，防止急性期病变恶化及缓解期复发，晚期采取对症和支持疗法，减轻神经功能障碍带来的痛苦。疾病修正治疗（disease-modifying therapy，DMT）主要包括：抗整合素α-4单抗（那他珠单抗 natalizumab），抗CD20单抗（奥瑞珠单抗 ocrelizumab、奥法木单抗 ofatumumab、利妥昔单抗 rituximab），抗CD52单抗（阿伦单抗 alemtuzumab）、干扰素（干扰素β-1a、干扰素β1-b）、富马酸类（富马酸二甲酯 dimethyl fumarate、富马酸单甲酯 monomethyl fumarate）、鞘氨醇调节剂（芬戈莫德 fingolimod、西尼莫德 siponimod、奥扎莫德 ozanimod）、免疫抑制剂（克拉屈滨 cladribine），还可使用其他免疫抑制剂如特立氟胺（teriflunomide）、硫唑嘌呤、环磷酰胺、米托蒽醌等。《OPERA I和OPERA II研究：复发相关的恶化与复发无关的进展对典型复发性多发性硬化症总体确认残疾积累的贡献》JAMA Neurology，2020年9月 (5)奥瑞珠单抗（ocrelizumab）是一种靶向CD20+B细胞的单克隆抗体，于2017年被批准用于多发性硬化的治疗。研究旨在评价复发相关的恶化（relapse-associated worsening，RAW）和复发无关的进展（progression independent of relapse，PIRA）对证实的残疾累积（confirmed disability accumulation，CDA）的影响，并评估两种治疗方法对预后的影响。这2个相同的、3期、多中心、双盲随机临床试验中，1656人纳入分析，两组平均年龄37.2-37.1岁，随机奥瑞珠单抗组（奥瑞珠单抗 600mg ivgtt q24w）或干扰素组（干扰素 ip q3w）共96周。12周后，干扰素组和奥瑞珠单抗组的残疾累积事件发生率分别为29.6%和21.1%；24周发生率分别为22.7%和16.2%。复发无关的进展事件是12周和24周复合残疾累积事件的主要影响因素，分别占干扰素组的78.0%和80.6%，占奥瑞珠单抗组的88.0%和89.1%。结论：大部分的残疾积累事件与明显的疾病复发无关，这挑战了目前多发性硬化复发和进展形式的临床区别。《ORATORIO研究的事后分析：奥瑞珠单抗治疗原发性进行性多发性硬化症的长期随访》Lancet Neurology，2020年12月 (6)ORATORIO研究是一项国际、多中心、双盲、随机对照的3期试验，招募年龄18-55岁的、原发性进行性多发性硬化症患者，随机分配奥瑞珠单抗（600mg ivgtt q24w）或安慰剂，至少120周，之后可以选择进入开放标签阶段。共451人进入完成6.5年的随访。在早期使用奥瑞珠单抗的患者，残疾进展比例较低（51.7% vs 64.8%，P=0.0018），复合进展率较低（73.2% vs 83.3%；p = 0.0023）；需要轮椅的比例较低（11.5% vs 18.9%；p = 0.0274）。在研究结束时，奥瑞珠单抗组患者T2病变体积更小（0.45% vs 13.00%， p

FDA 批准靶向PDL1抑制剂成为尿路上皮癌的一线治疗Clin J Am Soc Nephr 老年捐赠者单肾和双肾移植的应用和结果LANCET 供氧冷灌注与标准冷灌注保存肾脏的临床研究Am J Kidney Dis ABO血型不匹配的活体肾移植对患者生存的影响Nature子刊 使用血浆和尿液无细胞DNA甲基化模式识别肾细胞癌阿维鲁单抗（avelumab）2020年7月，FDA批准PD-L1抑制剂阿维鲁单抗（avelumab）用于局部晚期或转移性尿路上皮癌患者的一线维持治疗。《JAVELIN Bladder 100研究：阿维鲁单抗用于晚期或转移性尿路上皮细胞癌的维持治疗》New England Journal of Medicine，2020年9月 (1)这项3期试验的目的是阿维鲁单抗用于化疗后尿路上皮癌患者的维持治疗的疗效。研究纳入局部晚期或转移性尿路上皮细胞癌，并且一线化疗（吉西他滨+顺铂或卡铂治疗4~6个周期）后未出现疾病进展的患者共700人，随机分入支持治疗组、或阿维鲁单抗维持治疗组。阿维鲁单抗维持性治疗显著延长了总生存期和无进展生存期。阿维鲁单抗与对照组相比，1年总生存率分别为71.3%和58.4%（中位总生存期，21.4个月vs. 14.3个月；风险比，0.69；P=0.001）；在PD-L1阳性人群中，阿维鲁单抗组和对照组相比，1年总生存率分别为79.1%和60.4%（风险比，0.56；P

FDA 批准靶向PDL1抑制剂成为尿路上皮癌的一线治疗Clin J Am Soc Nephr 老年捐赠者单肾和双肾移植的应用和结果LANCET 供氧冷灌注与标准冷灌注保存肾脏的临床研究Am J Kidney Dis ABO血型不匹配的活体肾移植对患者生存的影响Nature子刊 使用血浆和尿液无细胞DNA甲基化模式识别肾细胞癌阿维鲁单抗（avelumab）2020年7月，FDA批准PD-L1抑制剂阿维鲁单抗（avelumab）用于局部晚期或转移性尿路上皮癌患者的一线维持治疗。《JAVELIN Bladder 100研究：阿维鲁单抗用于晚期或转移性尿路上皮细胞癌的维持治疗》New England Journal of Medicine，2020年9月 (1)这项3期试验的目的是阿维鲁单抗用于化疗后尿路上皮癌患者的维持治疗的疗效。研究纳入局部晚期或转移性尿路上皮细胞癌，并且一线化疗（吉西他滨+顺铂或卡铂治疗4~6个周期）后未出现疾病进展的患者共700人，随机分入支持治疗组、或阿维鲁单抗维持治疗组。阿维鲁单抗维持性治疗显著延长了总生存期和无进展生存期。阿维鲁单抗与对照组相比，1年总生存率分别为71.3%和58.4%（中位总生存期，21.4个月vs. 14.3个月；风险比，0.69；P=0.001）；在PD-L1阳性人群中，阿维鲁单抗组和对照组相比，1年总生存率分别为79.1%和60.4%（风险比，0.56；P

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.18.255885v1?rss=1 Authors: Zheng, H., Zhu, M. S., Liu, Y. Abstract: Circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of many diseases, including cancer. The genome-wide non-random fragmentation pat-terns of cfDNA are associated with the nucleosomal protection, epigenetic environment, and gene expression in the cell types that contributed to cfDNA. However, current progress on the development of computational methods and understanding of molecular mechanisms behind cfDNA fragmentation patterns is significantly limited by the controlled-access of cfDNA whole-genome sequencing (WGS) dataset. Here, we present FinaleDB (FragmentatIoN AnaLysis of cEll-free DNA DataBase), a comprehensive database to host thousands of uniformly processed and curated de-identified cfDNA WGS datasets across different pathological conditions. Furthermore, FinaleDB comes with a fragmentation genome browser, from which users can seamlessly integrate thousands of other omics data in different cell types to experience a comprehensive view of both gene-regulatory landscape and cfDNA fragmentation patterns. Availability and implementation: FinaleDB service: http://finaledb.research.cchmc.org/. FinaleDB source code: https://github.com/epifluidlab/finaledb_portal and https://github.com/epifluidlab/finaledb_workflow. Copy rights belong to original authors. Visit the link for more info

A liquid biopsy is a minimally invasive alternative to a more traditional surgical solid tumor biopsy. In this episode, Dr. Stephanie Hastings, genomics product lead at Q Squared Solutions, lays out the considerations for liquid biopsy collection and the type of information that can be gathered from circulating free DNA (cfDNA). The main approaches comprise for evaluating cfDNA are: specific mutation detection to help support targeted therapies broader sequencing technologies to enable biomarker evaluations custom sequencing panels to support clinical trial assay development She describes the typical panels for each of the approaches, the sample collection requirements and how these analyses are implemented on a global scale.

In episode 9 we dive deep into the topic that could not be more relevant today - diagnosis of infectious diseases. Our guest on this episode is Tim Blauwkamp, the co-founder and Chief Scientific Officer of Karius, a company that leverages genomics and AI to develop highly-accurate diagnostic tests based on cell-free DNA sequencing. Karius has recently raised a stunning Series B round of $165 million to further the transition of their test to clinic.Tim did his PhD in Biochemistry at the University of Michigan, where he studied genes involved in nitrogen assimilation in bacteria. He then continued as a PostDoc first in Michigan and then at Stanford researching the mechanisms behind WNT signaling and its role in cell differentiation. He then joined Moleculo as a Head of Molecular biology. Moleculo was acquired by Illumina and Tim was responsible for bringing to life the technologies that made it possible to generate long and accurate sequencing reads. About six years ago, Tim co-founded Karius together with Mickey Kertesz. Tim and his team have achieved enormous progress during the last years, bringing the diagnostic tests to clinics that are already changing the lives of patients. Together with Tim, we have talked about:: ◦ The story behind Karius ◦ Cell-free DNA (cfDNA) as a blood biomarker of infection ◦ Why DNA sequencing has an edge over classical microbiology methods ◦ The challenge of isolating microbial cfDNA from blood ◦ Untangling cfDNA sequencing data with AI ◦ Why Coronavirus (SARS-CoV-2) is hard to detect using NGS ◦ Diagnosing sepsis based on microbial cfDNA ◦ Clinical evidence as a key to healthcare innovation ◦ Working with payers to spread the use of innovative diagnostic tests ◦ How cfDNA screening can become a cornerstone of next-generation medicineGet in touch with Tim: ◦ LinkedIn: Tim Blauwkamp ◦ Twitter: @timblauwkamp ◦ Web (Karius): http://kariusdx.com/ ◦ Email: tim.blauwkamp@kariusdx.comMake sure to download the full show notes with our guest's bio, links to their most notable work and our recommendations for further reads on the topic of the episode at pmedcast.com

Dr. Sumanta K. Pal comenta o estudo apresentado por ele na ESMO 2019 que sugere que o cfDNA é uma opção de triagem secundária para estudos que avaliam terapias direcionadas ao FGFR3, como infigratinibe, em pacientes com câncer de bexiga metastático.

In 2011, cf DNA from the maternal serum became commercially available to screen for fetal aneuploidy. Overall, about 3% of test results will detect an aneuploidy, and false positive results are only seen in 0.05% to 0.1% of tests. Evolving data, however, suggest that in women who have more than one aneuploidy suspected by cfDNA testing but who are found by diagnostic testing to carry a genetically normal fetus may harbor a higher risk of occult maternal malignancy. In this session, we will review published data on the risk of maternal malignancy in women who have discordant cfDNA test results.

You have several options during your pregnancy when it comes to testing for chromosome abnormalities in your baby. The most common non-invasive screening tests are the first trimester screen and quad screen and these have been offered to all pregnant women for many years. With better technology comes more options for testing, especially when it comes to examining DNA. The cfDNA (cell free DNA) test, which became available in 2011, is named for the fragments of your baby’s DNA that are freely floating in your blood stream. This simple blood test from you can test for many more chromosome abnormalities than the traditional screen tests, plus the sex of your baby and their Rh factor. This episode breaks down everything you need to know about the cfDNA or NIPT test compared to other options so you can decide whether to opt in to this test and how to understand the results.   Show Notes: http://pregnancypodcast.com/nipt/   Thank you to Zahler for their support of this episode. Zahler makes a high quality prenatal vitamin that has the active form of folate, that I prefer after all of the research I have read on folic acid, plus it has omega 3s and DHA. This is the prenatal vitamin I take and the one I recommend. Zahler is offering an exclusive discount to listeners of the Pregnancy Podcast. To check out the vitamin and find out how you can save 25% when you buy a one month supply on Amazon go to http://pregnancypodcast.com/vitamin/

Prof. Massimo Cristofanilli shares his perspective on the future of liquid biopsy, the complementary purposes of CTC and cfDNA technologies, and when one should expect clinical utility of liquid biopsies. For more information, please visit http://www.NextGenerationDx.com/Circulating-Tumor-Cells/

Dr. Jorg Tost recently spoke to CHI to discuss his work with the ice-COLD-PCR assay and how it is addressing current challenges in cfDNA analysis. He also discusses challenges related to data, new technologies, and including other biomarkers in addition to cfDNA for the most complete and accurate analysis. Dr. Tost is speaking at the Enabling Technologies for Cell-Free DNA Analysis conference, part of Molecular Diagnostics Europe, taking place 22-24 May 2018 in Lisbon, Portugal. For more information, please visit http://www.MolecularDXEurope.com/Cell-Free-DNA-Technology/

Dr Salomon Manier speaks with ecancer at the 16th International Myeloma Workshop about cell-free DNA (cfDNA) and circulating tumour cells (CTCs) sequencing that enable serial temporal sampling. The team looked at whole-exome sequencing (WES) and ultra low pass-whole genome sequencing (ULP-WGS) of cfDNA and CTCs in multiple myeloma. The study demonstrated that WES and ULP-WGS of cfDNA and CTCs are consistently representative of tumour DNA alterations in terms of CNAs and SNVs. This approach could therefore be used to longitudinally follow clonal evolution and minimal residual disease in MM, personalising and improving treatment. It also reduces the need for bone marrow biopsy, greatly improving the patient experience.

Recently, there has been a push to develop alternative methods to traditional invasive techniques, such as solid tissue biopsies, for disease diagnosis and disease progression, as well as therapeutic response. Liquid biopsy is a new, minimally invasive technology for detecting circulating biomarkers without the need for costly or invasive procedures. Liquid biopsy enables users to sensitively, specifically and rapidly analyze circulating free nucleic acids (cfDNA), circulating tumor cells (CTCs) or exosomes from a blood sample. For more information please visit: http://bitesizebio.com/webinar/25528/liquid-biopsy-sample-handling/

Drs. Ben Solomon, Leora Horn, & Jack West assess the utility and limitations of "liquid biopsies", serum-based testing for molecular marker testing in lung cancer.

Drs. Ben Solomon, Leora Horn, & Jack West assess the utility and limitations of "liquid biopsies", serum-based testing for molecular marker testing in lung cancer.

Drs. Ben Solomon, Leora Horn, & Jack West assess the utility and limitations of "liquid biopsies", serum-based testing for molecular marker testing in lung cancer.

Dr. Jack West reviews new techniques for evaluating mutations from blood, including detection of circulating tumor cells (CTCs) or mutations in circulating free DNA (cfDNA) that can replace at least some tissue biopsies.

Dr. Jack West reviews new techniques for evaluating mutations from blood, including detection of circulating tumor cells (CTCs) or mutations in circulating free DNA (cfDNA) that can replace at least some tissue biopsies.

Dr. Jack West reviews new techniques for evaluating mutations from blood, including detection of circulating tumor cells (CTCs) or mutations in circulating free DNA (cfDNA) that can replace at least some tissue biopsies.