Podcasts about dana farber cancer institute

Dr. Cristina Pozo- Kaderman is the Director of the Young Adult Program at the Dana Farber Cancer Institute and just published her book COPING WITH CANCER IN EARLY ADULTHOOD, a book that talks about the many issues that young adults, beginning at age 19 have to go through. These issues have a wide variety of problems attached to them and Cristina writes about the many solutions for which this group of cancer fighters can choose from to help them live their best lives possible. 

This Editor's Special Episode of The HemOnc Pulse features Paul G. Richardson, MD, of Dana-Farber Cancer Institute, discussing treatment strategies for relapsed/refractory multiple myeloma and where selinexor-based regimens fit in today's evolving landscape. Drawing from real-world cases, Dr. Richardson explores care for patients before CAR T, after CAR T relapse, and in between—highlighting how selinexor can be used flexibly across multiple lines, including as a bridge to future immunotherapies. The conversation emphasizes individualized, dynamic treatment planning to balance disease control, tolerability, and long-term goals in an increasingly complex era of myeloma care.

In this episode of ASTCT Talks, supported by an educational grant from Sanofi US, Dr. Corey Cutler, from Dana-Farber Cancer Institute, and Dr. Guang-Shing Cheng, from the University of Washington and Fred Hutchinson Cancer Center, discuss how to identify and manage non-infectious lung complications following allogeneic transplant. From differentiating infection versus inflammation to managing conditions like organizing pneumonia (OP), this conversation offers practical insights for clinicians.For a deeper dive, explore Dr. Cheng's many publications on pulmonary topics in the Journal of Transplantation and Cellular Therapy. Additionally, read the article “Late-Onset Noninfectious Pulmonary Complications after Hematopoietic Stem Cell Transplantation” by Harris et al. shared in a September 2024 GVHD Supplement collection by the journal.

In this episode of ASTCT Talks, supported by an educational grant from Sanofi US, host Dr. Corey Cutler, MD, from Dana-Farber Cancer Institute, sits down with Dr. Sanjeet Singh Dadwal, MD, chief of infectious diseases at City of Hope, to explore a critical aspect of chronic graft-versus-host disease (GVHD): immune dysfunction and infection risk.The discussion highlights:• How chronic GVHD independently contributes to immune deficits and infection susceptibility.• Infectious risks associated with FDA-approved therapies for chronic GVHD.• Common infections in this population and why vigilance matters.• Practical guidance on prophylaxis strategies, vaccination timing, and navigating real-world challenges like food safety.This episode offers actionable insights for clinicians managing infection prevention and survivorship care in patients with chronic GVHD.Read “Infectious Disease Considerations in Chronic Graft-versus-Host Disease and Transplantation Survivors,” included in the 2024 GVHD Supplement collection published by Transplantation and Cellular Therapy.

In this episode of the Oncology Brothers podcast, we dived deep into the world of antibody drug conjugates (ADCs) in non-small cell lung cancer (NSCLC). We welcomed Dr. Jacob Sands from the Dana-Farber Cancer Institute to discuss the latest ADCs approved for NSCLC, including Trastuzumab deruxtecan (TDXd), Datopotamab deruxtecan (Dato-DXd), and Telisotuzumab Vedotin (Teliso-V). We explored the side effect profiles of these therapies, focusing on critical toxicities such as interstitial lung disease (ILD), mucositis, and peripheral neuropathy. Dr. Sands shared valuable clinical pearls on managing these adverse events, emphasized the importance of proactive monitoring and patient education. Key topics covered in this episode: • Overview of ADCs and their role in NSCLC treatment • TDXd: alopecia, ILD, fatigue, nausea/vomiting • Dato-DXd:  cytopenias, mucositis, dry eyes • Teliso-V: peripheral neuropathy, fatigue, peripheral edema • The evolving landscape of ADCs and future directions in lung cancer treatment Whether you're a healthcare professional or someone interested in oncology, this episode provides essential insights into the management of side effects associated with these innovative therapies. Tune in for practical advice and expert opinions that can enhance patient care in the community setting. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more episodes on practice-changing discussions in oncology! #ADC #NSCLC #TDXd #DatoDXD #TelisoV #ToxicityManagement #OncologyBrothers

While getting an annual mammogram is pretty commonplace for many women, the testing isn't always accessible for many reasons: language barriers, a lack of insurance or being underinsured, the inability to get to a clinic, and childcare issues, just to name a few. Dana-Farber Cancer Institute's Mammography Van has a solution for that. The hospital has packed up a full mammography suite into a van, making stops around Greater Boston to ensure everyone can get a scan who needs it. Tia Goodman, the Program Director for the Mammography Van, joins the show this week with details.See omnystudio.com/listener for privacy information.

Results of a phase II trial of olaparib in combination with ceralasertib in patients with recurrent and unresectable osteosarcomaOsteosarcoma Webinar Series: Katie Janeway, MD and Suzanne Forrest, MD join us on OsteoBites to discuss results of a phase II trial of olaparib in combination with ceralasertib in patients with recurrent and unresectable osteosarcoma.Dr. Janeway received her MD and MMSc from Harvard Medical School. She completed her pediatrics residency and her Pediatric Hematology-Oncology fellowship at Boston Children's Hospital and Dana-Farber Cancer Institute. She is an Associate Professor of Pediatrics, a Senior Physician who cares for young people with sarcoma, and Director of Clinical Genomics. Dr. Janeway's research is focused on precision oncology and bone sarcomas. She leads clinical trials both as an independent investigator and as the Chair of the Children's Oncology Group (COG) Bone Tumor Committee. The Janeway Laboratory leads several studies, which have enrolled and sequenced more than 2,500 patients with childhood cancers. They are using this data to deepen the understanding of clinical and genomic factors explaining prognosis and treatment response, and resistance, with a focus on sarcomas. In collaboration with Count Me In, the group is innovating patient partnerships in sarcoma research.Dr. Forrest completed her medical school training at Yale University, followed by pediatrics training in the Boston Combined Residency Program. She then pursued a pediatric oncology fellowship at Dana-Farber Cancer Institute / Boston Children's Hospital. Currently, she serves as an Assistant Professor of Pediatrics at Harvard Medical School and an Attending Physician in the Department of Hematology/Oncology at Dana-Farber / Boston Children's Cancer and Blood Disorders Center. Her research focuses on developing novel clinical trials that utilize cancer genomics to guide treatment strategies for pediatric solid tumors.After a short presentation on this research, they will take questions from attendees. Share your questions in advance with us at Christina@MIBAgents.org.

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. In this episode, Dr Matulonis sat down with guest Panagiotis (Panos) A. Konstantinopoulos, MD, PhD, to discuss the different subtypes of endometrial cancer and treatment developments for this disease. Dr Konstantinopoulos is the director of Translational Research in the Division of Gynecologic Oncology, the director of the Mellen and Eisenson Family Center for BRCA and Related Genes, and the Velma Eisenson Chair for Clinical and Translational Research at Dana-Farber Cancer Institute; as well as a professor of medicine at Harvard Medical School. Drs Matulonis and Konstantinopoulos explained that patients with mismatch repair–deficient (dMMR) tumors substantially benefit from a decreased risk of progression or death when immunotherapy is added to standard therapy. They noted that immunotherapy appears important for the management of dMMR tumors, even those in earlier stages or in patients who have no measurable disease remaining after surgery. For MMR-proficient (pMMR) tumors, Drs Matulonis and Konstantinopoulos highlighted that PD-1 blockade combined with chemotherapy improves survival vs chemotherapy alone, but that this benefit is not as substantial as that seen in dMMR disease. Crucially, they reported that if a pMMR tumor has no measurable disease after surgery, adding immune checkpoint blockade does not appear beneficial. They stated that tailored treatment approaches are key for managing pMMR disease subtypes. They added that hormonal therapy may be used upfront for slow-growing, estrogen receptor–positive metastatic disease. They continued by saying that DNA damage and replication stress are critical targets, particularly in p53-mutated tumors, like uterine serous cancers. Furthermore, they stressed that although the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) is highly effective in HER2-positive tumors, treatment with this agent requires monitoring for toxicities, including interstitial lung disease and decreased ejection fraction.

Dr. Alison Loren and Dr. Ann Partridge share the latest guideline from ASCO on the management of cancer during pregnancy. They highlight the importance of this multidisciplinary, evidence-based guideline and overarching principles for the management of cancer during pregnancy. Drs. Loren and Partridge discuss key recommendations from each section of the guideline, including diagnostic evaluation, oncologic management, obstetrical management, and psychological and social support. They also touch on the importance of this guideline and accompanying tools for clinicians and how this serves as a framework for pregnant patients with cancer. The conversation wraps up with a discussion on the unanswered questions and how future evidence will inform guideline updates.  Read the full guideline, "Management of Cancer During Pregnancy: ASCO Guideline" at www.asco.org/survivorship-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/survivorship-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-02115   Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Alison Loren from the Perelman School of Medicine of the University of Pennsylvania and Dr. Ann Partridge from Dana-Farber Cancer Institute, co-chairs on "Management of Cancer During Pregnancy: ASCO Guideline." Thank you for being here today, Dr. Loren and Dr. Partridge. Dr. Alison Loren: Thanks for having us. Dr. Ann Partridge: It's a pleasure. Brittany Harvey: And then just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Partridge and Dr. Loren who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into the meat of this guideline, to start us off, Dr. Loren, could you provide an overview of the scope and purpose of this new guideline on the optimal management of cancer during pregnancy? Dr. Alison Loren: Sure, thanks, Brittany. So this was really born out of I think a lot of passion and concern for this really vulnerable patient population. We have observed, and I am sure it is not any surprise to your audience, that the incidence of cancer in young people is increasing. And simultaneously, people are choosing to become pregnant at older ages, and so we are seeing more and more people with a cancer diagnosis during their pregnancy. And for probably obvious reasons, there is really no way to do randomized clinical trials in this population. And so really trying to assemble and articulate the best evidence for safely managing the diagnosis of cancer, the management of cancer once it is confirmed, being thoughtful about obviously the health of the mom, but also attending to potential risks to the developing fetus, and really just trying to be really comprehensive and balanced about all the choices for these patients when they are facing some really challenging decisions in a very emotionally fraught environment. And I think it is really emotionally fraught for the providers, too. You know, this is obviously an extremely intense, very emotional set of decisions, and so trying to provide a rudder essentially to sort of help people frame the questions and trying to make as evidence-based a set of recommendations as possible. Dr. Ann Partridge: And I would just add that "evidence-based" is a strong word here because typically our, as you just heard, our gold standard evidence is a randomized trial, but you can't do that in this setting, in general. And so, what we were able to do with the support of the phenomenal ASCO staff was to pull together kind of the world's literature on the safety and outcomes of treatments during pregnancy, as well as consensus opinion. And I think that is a really, really critical difference about this particular guideline compared to many of the other ones that ASCO does, where consensus and good judgment needed to kind of rule the day when evidence is not available. So, there is a lot of that in our recommendations. Dr. Alison Loren: That is such a good point. And I just, before we move forward, I just want to reflect that the composition of the panel was really broad and wide-ranging. We had maternal medicine specialists, we had legal and ethical experts, we had representatives who understand pharmaceutical industries' perspectives, and then medical oncologists representing the full spectrum of oncology diagnoses. And so it was a really diverse, in terms of expertise, panel, internationally composed to try to really get the best consensus that we could in the absence of gold standard evidence. Brittany Harvey: Absolutely. That multidisciplinary panel is really key to developing this guideline and, as you said, looking at the evidence and even though it does not reach the level of randomized trials, still critically evaluating it and reviewing that along with consensus to come up with optimal management for diagnosis and management of cancer during pregnancy. So then to follow that up, I would like to next review the key recommendations of the guideline across the main sections that the expert panel provided. First, I will throw this out to either of you, but what are the important general principles for the management of cancer during pregnancy? Dr. Ann Partridge: I think there were three major principles that we hammer home in the guidelines. One is that this is a team sport. It is multidisciplinary care that is necessary in order to optimize outcomes for the patient and potentially for the fetus. And that you really need to, from the beginning, bring in a coordinated team, including not just oncologists but obstetricians, maternal-fetal medicine specialists, neonatologists, ethics consultants, and obviously the patient and potentially her family. So that, I think, is one of the most important things. Second would be that obviously in a pregnancy, there are two potential patients and that the nuances of safety and risk from treatment is really wrapped up in where in the trimester of the pregnancy the patient is diagnosed, along with the kind of cancer that it is, both the urgency of treatment and the risk of the cancer, as well as the potential risks of any given intervention across the cancer continuum. It is a broad guideline in that regard. And then finally, and this is particularly timely given what is going on from a sociopolitical standpoint in the U.S., really thinking about informed consent and potential ethical as well as legal implications of some of the choices that patients might have when they are thinking about, in particular, continuing a pregnancy or potential termination. Dr. Alison Loren: And I will just add that I think that the key to all of this guidance is nuance and individualization and also making sure that patients and their care providers understand all the choices that are available to them and also the consequences of those choices. You know, nobody would choose to receive chemotherapy during pregnancy if that wasn't necessary. So there are risks to treatment, but there are also risks to not treatment. And making sure that in a suboptimal situation where you do not have a lot of evidence, trying to weigh, the best you can, the risks and benefits of all of the choices so that the patient can come to a decision about the treatment plan that is right for her. Brittany Harvey: Definitely. And those core concepts really set the stage for individualized care on what is necessary for appropriate multidisciplinary care, prioritizing both patient autonomy and informed decision making. With those core concepts and key principles in mind, I would like to move into the recommendations section of the guideline. So what are the key recommendations regarding diagnostic evaluation for pregnant patients with signs or symptoms of cancer? Dr. Alison Loren: I think the most important thing is to not delay, that there are very careful and well-thought-out recommendations for how to evaluate a potential cancer. And while there are certain things that we know can be harmful, particularly when certain dose thresholds are exceeded - for instance, abdominal imaging, there are certain radiographic thresholds that you don't want to exceed because of risk of harm to the embryo or fetus - there are still lots of options for diagnosing cancer during pregnancy. And again, thinking about the costs of not doing versus the cost of doing, right? It is really important to make the diagnosis of cancer if that is a consideration or a concern. And sometimes going directly to biopsies or getting definitive studies, even if there is a small risk to the developing fetus, is really essential because if the mom does not survive, of course, the fetus is also not going to survive. And so we need to be thinking first about the patient who is sitting in front of us, the woman who needs to know what is going on in her body so she can make good decisions about her health. So, I think that is a key principle in thinking about this. Brittany Harvey: Absolutely. So, following that diagnosis of a new or recurrent cancer, what is recommended for oncologic management of patients who are diagnosed with cancer during their pregnancy? Dr. Ann Partridge: So, I think the general principle is, again, cancer is such a wide number of diseases and even within diseases, a range of stages and risks and associated opportunities for risk reduction and/or treatment depending on the type of cancer. Just by example, in the work that I do, which is breast cancer, once someone has had a surgery in the early-stage setting, a lot of our treatment is about risk reduction. And that is very different than from what Alison does, which is treating people with leukemia, where it is kind of binary. If you do not treat, including with cytotoxic drugs, the patient and an unborn fetus will die, especially early in the pregnancy, obviously. So this is where cancers are very, very different. So I think taking the approach of what would you do if the patient were not pregnant? And what is the best treatment for that particular patient with that particular kind of cancer? And then applying the pregnancy and where the patient is in that pregnancy in terms of the trimester of the pregnancy, and what is safe and what is unsafe from the options that you would give her if she were not pregnant. And then if the patient is choosing to keep the pregnancy, which in my practice, many people come and they come to me because they want to hold onto their pregnancy and want to figure out how to make it work, coming up with a regimen that tries to give them kind of the best bang for the buck, the best possible breast cancer therapy with the least harm, when possible, to the fetus. It is a bit of a balance, right? And then we cannot always give people the best approach. And sometimes it comes down to making a decision to give up something that may improve their survival so as not to harm the fetus. And sometimes it goes the opposite direction where a patient will say, "Oh, that is going to improve my survival by 5% and you can't give it to me now? I am going to choose to terminate." Even though that is obviously a very, very difficult and challenging decision to make in this setting because they want to optimize their survival and ideally live on to potentially have another pregnancy in the future if that is something that is of interest to her. So these are really, really hard conversations as you can imagine, but that is kind of where we go. Dr. Alison Loren: Yeah, and I think this is where the need for more research and understanding is really key because sometimes questions come up. I guess I am thinking about like HER2-directed agents, which we know are contraindicated in pregnancy. But what about sequencing? Does it matter when you get it? Can you get it later? I think that is something that we don't really fully understand. And similarly, again, this is obviously like a breast cancer and blood cancer focused discussion because that is what we do, but thinking about managing blood cancers, certainly with acute lymphoblastic leukemia, there is actually a lot of options now that, you know, you could potentially use to temporize or sort of get somebody through a pregnancy relatively safely. I am focusing on the word "relatively" because we do not know what the long-term impact might be of potentially not optimal therapy in the long run. And then thinking about other things like timing of a bone marrow transplant relative to either delivery or termination. I mean, again, we really do not know what are the right sets of sort of timing considerations for those. So there are just a lot of unknowns. And I think trying to be sort of self-aware and humble and honest about those unknowns so that the patient can engage in the conversation in a way that is meaningful to her and make the decisions that make the most sense for her. I think the most important thing is to make sure that the patient feels supported and safe to make those decisions with as little regret as possible. Brittany Harvey: Yes, I think it is really important that you mentioned that there is a wide range of cancers here, and that means that care really needs to be individualized for each patient. I will also note, just in this section, that I found really informative while reading through the guideline the list of oncologic agents that may be offered in each individual trimester, whether it is contraindicated or it can be used with caution, or if there is relatively good safety data on it for prioritizing maternal treatment needs and balancing fetal safety at the same time. I think that is, that is really key. And I think readers will really like that section of the guideline to provide concrete information for them and their patients. Dr. Alison Loren: Thank you. We actually spent a lot of time on that table and just thinking about what it should look like, what the format ought to be, what the language ought to be. Because of course, at the end of the day, everything should be used with caution. So what does that actually mean? And we sort of tried to explicate that a little bit in like the footnotes. We really tried to leverage what we know from clinical experience, from package labels, from mechanism of action to try to be as clear and definitive as we could be without overstating or understating what we know. Dr. Ann Partridge: Yeah, and I think we are focusing on breast and leukemia because that is what we do. But the truth is much of the data comes from those two areas. Leukemia, not because it is so common, but because you do not really have choices to treat or not treat. And so for decades, they have been treating and saying, "We hope the progeny comes out okay." And for many agents it does. The babies are okay. And so, we have reasonable observational data. And then in breast cancer, there have been actually some prospective registry-type studies where people have been followed and treated when pregnant, and the progeny have been accounted for, and so we have some good experience in that way too. Again, not randomized trials, but at least data that suggests certain agents are safe. And increasingly, because of that, when we have had to treat patients, we have said, "Okay, let us do it on this registry so that we can at least learn from every patient that comes in in this situation." And so, I think we will have more and more data given the growing number of young adults with cancer and the delays in childbearing that are happening around the world, and particularly in Westernized countries. I wish we did not. We wish we did not see this problem, but of course, when we do, we have to make sure that we learn from it and try and get patients enrolled in these registries and any kinds of studies that are available. Dr. Alison Loren: Yeah, I will just underscore that to say that, you know, there is outcomes of pregnancy and then there is outcomes of pregnancy, right? So there is like, "Okay, the baby was born with 10 fingers and 10 toes, and they passed their Apgar, and they are doing all their developmental processes along the way." But what happens when they are 10 or 15 or 20? Are they maturing normally? Are they cognitively intact? And then, of course, it is really inseparable from what is the impact on a family of having the mom with cancer? And how does that impact childhood development and intellectual development? And so these are really, really important questions that are very difficult to answer given the longitudinal information that you need, but it is a really critical question that, you know, patients ask and we do not know the answer. Dr. Ann Partridge: Yeah, that actually leads me to one of the important principles in the guideline that is a little bit of a change from when I first started practicing, which is we have learned from the wider neonatology literature, as they have followed up on the children that were born prematurely, that it is actually better not to be premature and to keep the baby in utero as long as it is safe for the fetus and the mother as long as possible, ideally to term rather than delivering early and then giving the chemo after that or separating the chemo from before and after. We used to try and deliver early and then give agents, but now we typically will give agents that are safe to be given at the end of pregnancy, ideally close to term, a couple weeks out, to allow for the ability of count recovery, and you do not want to go into preterm labor with chemotherapy on board, but we used to go much earlier and have an argument with our maternal-fetal medicine doctors. "How early can you get them out?" And they would say, "How long can they stay in?" And increasingly, we have been able to try and compromise to go even later and allow the fetus to go to term because of the neonatal outcomes that in longer term there is a suggestion that the children are developing better in the long run if they are kept in utero for as long as possible. Dr. Alison Loren: Yeah, that is such a great point. I think that is probably the most important thing for people to take away. For anyone who sort of does this, I mean, no one does this regularly because it is a rare event, although I think it is increasing as I mentioned. But this idea that the third trimester is, most of us know, is primarily a time for growth. Most of the critical development has already occurred, and so administering most chemotherapy agents towards the end of the third trimester seems to be preferable long term than delivering them early. So that is a really big change. I think we used to try to sort of, "Oh, get them to 30 or 32 weeks and then deliver," but we really are trying to get them closer to term, 37 weeks or more, and then coordinating the treatment so that they are not nadiring, as Ann said, at the time of planned delivery. Brittany Harvey: Yes, and that is a really important point related to evidence-based care and why we have changed that practice. And so then that actually leads nicely into my next question. But as you both mentioned, this is an important collaboration between oncologists and obstetricians. So the next section of the guideline addresses obstetrical practice. And so beyond what is standard, what additional recommendations are there in obstetrical management for pregnant patients with cancer? Dr. Alison Loren: That is a great question. So I will say we were really struggling with like how much do we cover? Like this is an oncology guideline. We are not obstetricians. We certainly had great representation from our maternal-fetal medicine colleagues on the panel. But really trying to sort of give useful information without overstepping. And so I think that the main recommendations are to increase the frequency of fetal monitoring, make sure that there is close attention to blood counts in the patient. But I think there is really still a gap in terms of what we know about optimal management of a pregnant person who is receiving therapy and how to handle the pregnancy itself. The delivery should be a usual delivery. Our colleagues did not recommend a planned C-section. They recommended usual care in terms of planning for the delivery. Obviously, if a C-section is indicated, then it should be done, but it should not be planned this way because of the cancer diagnosis. And I guess the other thing that we mentioned in the guideline, although we were reluctant to push it too hard because of access to these specialized services, was evaluating the placenta after birth to ensure that there were no metastases in the placenta itself. Dr. Ann Partridge: Those are the main things, and judicious and prudent obstetrical care, as I think, you know, is trying to be practiced regularly with MFM. Typically these patients should be followed not by your average OB/GYN, but a maternal-fetal medicine specialist because these patients will have special concerns, especially if they are sick. So oftentimes, especially Alison's patients, are actually sick with leukemia. And so you are monitoring them a lot, whereas, you know, a breast cancer patient typically isn't sick, although they could get sick with their chemotherapy. And so we really want to hand-in-hand manage these patients with our MFM colleagues. Dr. Alison Loren: I think we also highlighted in the guideline just for the refresher purposes of the oncology community, generally which drugs that would be given in a normal oncology setting are safe to be given to a pregnant person. So we talked a little bit about what kinds of steroids are recommended, antiemetics, DVT prophylaxis, peripartum. These are things that we think about a lot in oncology, but just want to make sure that it sort of intersected appropriately with the care of a pregnant patient. Brittany Harvey: Definitely. That specialized care is really important for patients who are pregnant and have cancer. And then the last section of the recommendations addresses psychological and social support. As you both mentioned before, this is a highly emotional time and it can be difficult and challenging to make decisions. So what is recommended for the psychological and social support of pregnant patients with cancer? Dr. Ann Partridge: Well, as I said, it is really something that needs to be considered at the beginning, through the diagnostic period, all the way into survivorship. Ironically, even though it is a highly fraught, emotional situation, I find that my pregnant patients actually are extraordinarily resilient, and what they are really focused on often is the safety of the fetus, because again, many of the people that come to me, it is a highly wanted pregnancy. They are also focused on their own health, of course, and often you need to bring in social work, sometimes a psychologist, professionals who are there just to help manage their emotions while we are focusing on what do they need medically to be as healthy as possible, both for the again, the mother, the patient, and the fetus. It is very tricky, and I will say also bringing in sometimes people on the ethics team in the hospital to help, both from the "Are you recommending and giving something that is safe?" That is number one. And then number two, sometimes patients want to be treated with drugs that we do not have any safety data for in pregnancy. What are our obligations? I think most of us would say we would not treat someone if we do not have safety data and there is suspicion for concern. But where is that line in terms of the right thing to do by that patient? And so we are all beholden to our ethics colleagues to help us when we make decisions like that. You know, we all want to do right by the patient, but we have to uphold our oaths and legal obligations. I don't know if you have to add on that because it's very tricky. Dr. Alison Loren: It is, it is very hard. I mean, I think, you know, there is a lot of emotion, obviously any cancer diagnosis is extremely charged and people are already at sort of a heightened, you know, they are anticipating a new baby and planning around that. And so it is just an extremely disruptive is the smallest word I can think of to describe it. And I think that often there is a co-parent, there might be parents and in-laws and other siblings, and then there is care after delivery. And so it is just a very complex set of dynamics. And having both our ethics colleagues and our psychology and social work colleagues to sort of just pitch in and make sure that the patient is being supported. I think there are sometimes really difficult situations where maybe what the patient wants is different from what the father of the baby wants or what the rest of the family wants. And so that can be really challenging. And you never really know where those landmines are going to pop up. So it is good to have the team on board early and often. Dr. Ann Partridge: Yeah, I would add to that, the other thing here that I think is really important, like in all of medicine but especially in situations like this, this is where we have to be very careful as professionals not to impose our own ethical, moral, emotional, personal views on the patient and to try to reserve judgment as much as possible. We are their navigator with the most important evidence and information that we can provide in the current situation. And that is where this guideline is extraordinarily helpful, we hope, for clinicians in the years to come. And at the same time, we cannot necessarily impose our own views and what we would do on a patient or what we tell our daughters, sisters, friends, family members. It is very tricky in that way. And so sometimes not just support for the patient, but support for the care team may be warranted in some of these very fraught situations. Dr. Alison Loren: Yeah, that is such a great point. And I was sort of thinking that too. I mean, it is, of course, the patient is front and center, but these are really difficult situations to navigate. And I will just add also that a lot of times these patients end up in academic centers, which I think is that's where the expertise or even just the experience may be. But the downside of that is that, you know, the teams are constantly changing. You have a new resident, you have a new intern, you have a new attending, a new fellow. And so, you know, the patients may be subjected to lots of different ways of communicating and sometimes those perceived differences can be really challenging. So sort of team huddles to sort of make sure that everybody is reading from the same script and everyone is comfortable with how the information is being presented so that the patient does not feel more confused or more overwhelmed, that they are kind of getting a consistent message from the whole team that, "This is what we know, this is what we are recommending, here are your other choices, and here are the pros and cons of each of these options." Brittany Harvey: Yes, I think you have both touched on this and that bringing in appropriate experts to support both clinicians and patients and their decision-making and their mental health is really important for this section of the guideline. We have already discussed this a fair bit throughout our conversation, but in your view, what is the importance of this guideline and how will it impact both clinicians and pregnant patients diagnosed with cancer? Dr. Ann Partridge: I could start with that. We just talked about experts and having them all around, but the fact is most people do not have the experts all around when they are dealing with this. And I think this is, you know, an expert-based, evidence-based guideline where having this in one's back pocket, whether you are in rural Montana or at a major cancer center on either coast, you will be armed with the latest and the greatest in terms of what we know and what we do not know, and some very helpful algorithms for how to think through the process of dealing with a patient who is diagnosed during pregnancy, whichever type of cancer it is. We could not cover every single specific thing about every cancer, although it is a pretty long guideline and there is a lot of nuance in there. So you might find a lot about specific cancers. And I think that that will be very, very helpful for people who are faced with this situation in the clinics just to frame it out, think through. Sometimes there is no answer that is the perfect answer and then, you know, using this as kind of a scaffolding and phoning a friend who may have more experience to help guide you and guide the patient, most importantly. I think it will be very helpful in that regard. Dr. Alison Loren: Yeah, I think so too. And I have talked about that we are working on this guideline and the anecdotal feedback has been, "This is so helpful." Like there really has not been, I think, an all-in-one place, diagnostic considerations, radiographic considerations, staging, treatment, all the modalities, surgical, radiation, systemic chemotherapy. We tried to include, when we could, novel agents including targeted agents and monoclonal antibodies and bispecifics and cellular immunotherapies and non-cellular immunotherapies. We really, really tried to cover in 2025 what are people using to treat cancer and to try to give the most balanced view of what we think is is safe or reasonably safe and what we think is either unproven or known to be risky, really to have it be kind of a go-to, like all-in-one, as much information as we have about these really challenging cases. We tried to include, Ann mentioned, you know, specific cancers, and I think when there were specific things to shout out with specific cancers, we really tried to highlight that. Like, "Okay, lots of young patients with cancer have Hodgkin's lymphoma, so what is safe and what is not for that specific case?" Or, "What is safe or what is not when you are thinking about colon cancers?" And we have a shout-out in here about considering checking for DPD deficiencies in patients who are pregnant. And I know it is generally recommended nowadays, but certainly for people who are pregnant, you know, you really want to avoid excess toxicity. So I think just really trying to be attentive to specifics about certain cancers in young patients and what would be valuable for a practicing oncologist and obstetrician to know when you are faced with this situation. Dr. Ann Partridge: Yeah, and I think the other critical thing that is great about this guideline is it's a starting place. And I anticipate that we will be building on this guideline for many years to come. And remember that when first, I was not around then, but probably three or four decades ago, when chemotherapy was just coming out and patients were coming in pregnant, there was a feeling I am sure that was, "We cannot give this to this person because it is purposefully going to destroy cells. And when you destroy cells in a growing fetus, you are going to destroy or harm that fetus." And yet, people did not have great choices. It was get treated or die, especially with things like leukemia early on. And bold patients along with their oncologist said, "Bring it on." And that is how some of this literature has been born. And so moving forward, there will be either purposeful exposures or inadvertent exposures of some of our therapies where we will learn ultimately. And this is a place where we can update these guidelines. That is the beautiful thing about the ASCO guidelines is that they are constantly being thought about to be updated. And then when there is enough of a change in practice, they will be updated such that they will continue to inform how we do this in the years to come for patients who come in pregnant. Dr. Allison Loren: Yeah, and I will say I have been doing this long enough now, we were just talking about a different guideline, the fertility guideline earlier today, and over the 20 years that the fertility guidelines have been out, just the amount of research has really skyrocketed. And you can see as you look at each guideline how much we have learned, what we can say, "Yes, this is working," "No, this is not working." Like, it is stuff that we used to say, "Oh, we do not really know," and now we have answers.  I think I speak for both of us when I say that we are hopeful that this will serve as, as Ann said, as a starting off point and really inspire people to ask the questions and do the research so that we can give better guidance moving forward, really trying to think about, you know, mechanisms and leaning on our colleagues in pharma and in the government who sort of think about safety and efficacy, to sort of make sure that they are contemplating not just non-pregnant patients, but also pregnant patients or as they are thinking about marking the package inserts with safety guidelines around this. Brittany Harvey: Yes, this is a critically important first guideline on the management of cancer during pregnancy, and we will look forward to continuing to build on that. I think as you mentioned, this guideline is far-reaching and has a lot of recommendations in it. And so both the full text of the guideline and those at-a-glance algorithms, figures, and tables will be really useful for clinicians in their clinic. Finally, to wrap us up, we have just been discussing this a little bit, but specifically, what are the outstanding questions on the management of pregnant patients with cancer, and where is this further research needed? Dr. Alison Loren: There are lots and lots and lots of unanswered questions. And I think if you look at the table, most of what we say is, "We are pretty sure this is okay, we are not so sure about this." I am paraphrasing, but we really just are operating in a paucity of what we would normally consider gold-standard evidence. It is hard to imagine, of course, there would ever be, as we mentioned in the beginning, randomized trials. But I think that preclinical data, mechanistic data, trying to think about including as we go through animal data, making sure that we are looking at female animals and pregnant animals so that we can sort of fully understand what the impact may be. And then I think thinking about more localized therapies around sort of radiation, you know, we are now moving into really hyper-focused radiation treatments like protons. Is that better because there is less scatter? Like I think those are real considerations that we just do not know the answer to. What do you think? Dr. Ann Partridge: I think so many unanswered questions, and this is a call to action to continue to and increase the documentation of the experiences and outcomes for patients diagnosed during pregnancy. Dr. Alison Loren: Yeah, and I think the long-term outcomes too are really going to be critical. Brittany Harvey: Yes, we will look forward to learning about more evidence across the spectrum of care to inform future updates to this guideline. So I want to thank you both so much for your work to develop this guideline, to review the extensive amounts of literature that you did, and work to create this guideline. And thank you also for your time today, Dr. Loren and Dr. Partridge. Dr. Alison Loren: Thanks. It was fun. Dr. Ann Partridge: Yeah, thank you. Brittany Harvey: And 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/survivorship-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 

In this country, health outcomes are too often dictated by your ZIP code, but one company is working very hard to fix those inequities.Demond Martin, is the CEO and co-founder of WellWithAll, a health and wellness company dedicated to advancing health equity for underserved communities. Operating under ‘inclusive capitalism', WellWithAll reinvests 20% of its profits into health initiatives tailored to specific community needs, tackling health disparities, and ensuring a targeted approach to wellness.Before WellWithAll, Demond was a senior partner at Adage Capital Management, where he invested in the consumer sector for 21 years. Earlier in his career, he served in the Clinton administration, and he has served on numerous nonprofit boards, including the Berkeley College of Music, The Dana-Farber Cancer Institute, and the Obama Foundation. Today, we get into what WellWithAll does, how they're giving back to the community, and Demond's journey from a trailer in North Carolina to CEO of this incredible company.Highlights:Demond's background (2:21)Stories from the White House (3:50)Working at a hedge fund (5:58)Lessons about investing (8:32)The origins of WellWithAll (11:42)Health inequities (13:54)How WellWithAll has evolved (15:08)Getting in with large retailers (17:08)Sources of funding (18:57)The Obama Foundation (20:19)A career in politics? (21:00)Demond's mentors (22:14)27th ICR Conference (24:04))Links:Demond Martin LinkedInWellWithAll LinkedInWellWithAll WebsiteICR LinkedInICR TwitterICR WebsiteFeedback:If you have questions about the show, or have a topic in mind you'd like discussed in future episodes, email our producer, joe@lowerstreet.co.

JCO Editor-in-Chief Dr. Jonathan Friedberg is joined by colleagues Dr. Jennifer Woyach, Dr. Wojciech Jurczak, and Dr. Matthew Davids to discuss simultaneous publications presented at ASH 2025 on pertibrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Jonathan Friedberg: I'm Jonathan Friedberg, editor of Journal of Clinical Oncology, and welcome to JCO After Hours, where we are covering two manuscripts that were presented at the American Society of Hematology meeting 2025 in Orlando, Florida. I am delighted to be joined by colleagues on this call to discuss these pivotal manuscripts which cover the topic of pirtobrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. I will first just introduce our guests, Dr. Woyach. Dr. Jennifer Woyach: Hi, my name is Jennifer Woyach. I am from the Ohio State University. Dr. Wojciech Jurczak: Hello, I am Wojciech Jurczak, working at the National Research Institute of Oncology in Krakow, Poland. Dr. Matthew Davids: Hi, I am Matthew Davids from Dana-Farber Cancer Institute in Boston. Dr. Jonathan Friedberg: We are going to start by just learning a little bit about these two trials that were both large, randomized phase 3 studies that I think answered some definitive questions. We will start with your study, Jennifer. If you could just describe the design of your study and the patient population. Dr. Jennifer Woyach: Absolutely. So this is the BRUIN CLL-314 study, and this is a phase 3 randomized trial of pirtobrutinib versus ibrutinib in patients with CLL or SLL who had not previously been treated with a covalent BTK inhibitor. The patients were both treatment-naive and relapsed/refractory, about one-third of the patients treatment-naive, the rest relapsed/refractory, and they were stratified based upon 17p deletion and the number of prior lines of therapy. The primary objective was looking at non-inferiority of overall response rate over the entire treated population as well as the relapsed/refractory patient population. Key secondary objectives included progression-free survival in the intention-to-treat and the smaller relapsed/refractory and treatment-naive populations. Dr. Jonathan Friedberg: And just comment a little bit on the risk of the patients. Dr. Jennifer Woyach: This study was fairly typical of this cohort of patients. Within the relapsed/refractory patient population, there was a median of one prior line of therapy in each of the groups, up to nine prior lines of therapy in the patients included on the study. For the overall cohort, about two-thirds of the patients were IGHV unmutated, about 15% had 17p deletion, 30% had TP53 mutations, and about 35% to 40% had a complex karyotype, which is three or more abnormalities. Dr. Jonathan Friedberg: And what were your findings? Dr. Jennifer Woyach: Regarding the primary outcome, which is the focus of the publication, we did find that pirtobrutinib was indeed non-inferior and actually superior to ibrutinib for overall response rate throughout the entire patient population and in both the relapsed/refractory and treatment-naive cohorts. PFS is a little bit immature at this time but is trending towards also being significantly better in pirtobrutinib-treated patients compared with ibrutinib-treated patients. Probably most significantly, we found this to be the case in the treatment-naive cohort where there was a striking trend to an advantage of pirtobrutinib versus ibrutinib. Dr. Jonathan Friedberg: And the follow-up that you have on that progression-free survival? Dr. Jennifer Woyach: So we have about 18 months follow-up on progression-free survival. Dr. Jonathan Friedberg: The second study, Wojciech, can you just go through the design and patient population that you treated? Dr. Wojciech Jurczak: Thank you, Dr. Friedberg, for this question. So the BRUIN CLL-313 study was, in fact, the first phase 3 study with pirtobrutinib in exclusively untreated CLL patients. It was a randomized study where we challenged pirtobrutinib versus bendamustine-rituximab. At the time we designed the protocol, bendamustine-rituximab was an option as a standard of care, and Bruton tyrosine kinase monotherapy was used far more commonly than nowadays. The primary target of the study was progression-free survival. We took all untreated patients except for those with 17p deletions. Therefore, it is a good representation for intermediate risk. We had about 60% of the population, 56 to be precise, which was unmutated, evenly distributed into two treatment arms. 17p deleted cases were excluded, but we had about 7% and 8% of TP53 mutated patients as well as about 11% and 7%, respectively, in the pirtobrutinib and bendamustine-rituximab arm of patients with complex karyotype. The progression-free survival was in favor of pirtobrutinib and was assessed by an independent review committee. What is important is that the progression-free survival of the bendamustine-rituximab arm was actually similar to the other studies addressing the same questions, like the comparison with ibrutinib in the ALLIANCE study or zanubrutinib in the SEQUOIA study. What was different was the hazard ratio. In our study, it was 0.20. It was one of the longest effect sizes noted in the frontline BTK study. It represented an 80% reduction in progression-free survival or death. If we compare it to ibrutinib or zanubrutinib, it was 0.39 and 0.42 respectively. Presumably, this great effect contributed towards a trend of overall survival difference. Although survival data are not mature enough, there is a clear trend represented by three patients we lost in the pirtobrutinib arm versus 10 patients lost in the bendamustine-rituximab arm. This trend in overall survival is becoming statistically significant despite the fact that there was a possibility of crossover, and effectively 52.9 patients, which means 18 out of 34 patients relapsing in the bendamustine-rituximab arm, were treated by pirtobrutinib. Dr. Jonathan Friedberg: I am going to turn it over to Matt. The question is: why study pirtobrutinib in this patient population? And then with these two studies, how do you find the patients that were treated, are they representative of people who you see? And do you see this maybe being approved and more widely available? Dr. Matthew Davids: I think in terms of the first question, why study this in a frontline population, we have seen very impressive data with pirtobrutinib in a very difficult-to-treat population of CLL patients. This was from the original BRUIN phase 1/2 study where most of the patients had at least two or three lines of therapy, often both a covalent BTK inhibitor and the BCL2 inhibitor venetoclax, and yet they were still responding to pirtobrutinib. The drug was also very well tolerated in that early phase experience. And actually, we have seen phase 3 data from the BRUIN 321 study comparing pirtobrutinib to bendamustine and rituximab in a relapse population as well. So I think that really motivated these studies to look at pirtobrutinib as a first therapy. You know, often in other cancers of course, we want to use our best therapy first, and I think these studies are an initial step at looking at that. In terms of the second question around the patient population, these are pretty representative patient populations, I would say, for most frontline CLL studies. We see patients who are a bit younger and fitter than sort of the general population of CLL patients who are treated in clinical practice, and I think that is true here as well. Median age in the sort of mid-60s here is a bit younger than the typical patients we are treating in practice. But that is not different from other CLL frontline studies that we have seen recently, so I think it makes it a little bit easier as we kind of think across studies to feel comfortable that these are relatively similar populations. Dr. Jonathan Friedberg: How do you see this either getting regulatory approval or potentially being used compared to current standard of care options? Dr. Matthew Davids: So my understanding is that both of these trials were designed with registrational intent in the frontline setting, and they are both positive studies. That is certainly very encouraging in terms of the potential for an approval here. We have seen in terms of the FDA recently some concerns around the proportion of patients who are coming from North America, and my understanding is that is relatively low on these two studies. But nonetheless, the datasets are very impressive, and so I think it is certainly supportive of regulatory approval for frontline pirtobrutinib. Dr. Jonathan Friedberg: I will ask Jennifer a question. The control arm in your study was ibrutinib, and I think many in the audience may recognize that newer, second-generation BTK inhibitors like acalabrutinib and zanubrutinib are more frequently used now if monotherapy is decided. How do you respond to that, and how would you put your results in your pirtobrutinib arm in context with what has been observed with those agents? Dr. Jennifer Woyach: Yeah, that is a great question. Even though in the United States we are predominantly using acalabrutinib or zanubrutinib when choosing a monotherapy BTK inhibitor, this is actually not the case throughout the entire world where ibrutinib is still used very frequently. The head-to-head studies of both acalabrutinib and zanubrutinib compared to ibrutinib have shown us pretty well what the safety profile and efficacy profile of the second-generation BTK inhibitors is. So even though we do not have a head-to-head study of acalabrutinib or zanubrutinib versus pirtobrutinib, I think, given the entirety of data that we have with all of the covalent BTK inhibitors, I think we can safely look at the pirtobrutinib arm here, how the ibrutinib arm compares or performs in context with those other clinical trials. And though we really can not say anything about pirtobrutinib versus acalabrutinib or zanubrutinib, I think we can still get a good idea of what might be the clinical scenarios in which you might want to choose pirtobrutinib. Dr. Jonathan Friedberg: And Wojciech, do you agree with that? Obviously, I think you have acknowledged that chemoimmunotherapy is rarely used anymore as part of upfront treatment for CLL. So, I guess a similar question. If you were to put the pirtobrutinib result in your study in context with, I guess, more contemporary type controls, would you agree that it is competitive? Dr. Wojciech Jurczak: Well, I think that that was the last study ever where bendamustine-rituximab was used as a comparator arm. So we should notice that smashing difference. Because if we look at the progression-free survival at two years, we have 93.4% in pirtobrutinib arm versus 70.7% in bendamustine-rituximab arm. Bendamustine-rituximab arm did the same as in the other trials, like ALLIANCE or SEQUOIA. Pirtobrutinib did exceptionally well, as pirto is not just the very best BTK inhibitor overcoming the resistance, but perhaps even more important for the first line, it is very well tolerated and is a very selective drug. Now, if we look at treatment-related adverse events, the discontinuation rate, they were hardly ever seen. If we compared the adverse events in exposure-adjusted incidence, literally all adverse events were two or three times higher in bendamustine-rituximab arm except for the bleeding tendency, which however was predominantly in CTCAE grade 1 and 2 with just 0.7% of grade 3 hemorrhage. Therefore, I think that we should actually put the best and the safest drugs upfront if we may, and pirtobrutinib is, or should be, the first choice if we choose monotherapy. Now, I understand that we are not presenting you the data of pirtobrutinib in combination with anti-CD20 or with BCL2 inhibitors, but that is to come. Dr. Jonathan Friedberg: Matt, how would you envision, were regulatory approval granted and this were an option, using this in the upfront patient population? Is there anybody who you would preferentially use this or start on this treatment? Or would this be something that you would tend to reserve for second line? Dr. Matthew Davids: So I would say that in general for most of my patients who would want to start with a continuous BTK inhibitor, I would still use a covalent BTK inhibitor, and I say that for a couple of reasons despite the very promising data from these studies. The first is that the follow-up for both of these phase 3 trials is still quite short, in the range of a median 18 to 24 months. And we know that CLL is a marathon, not a sprint, and these patients are going to probably be living for a very long time. And we do have much longer follow-up from the covalent BTK inhibitors, median of 10-year follow-up with ibrutinib and five to six years with zanubrutinib and acalabrutinib respectively. And you know, I do not think that the pirtobrutinib is going to fall off a cliff after two years, but on the other hand, I think there is a lot of value to long-term data in this disease, and that is why I think for most of my patients I would stick with covalent BTK inhibitors. But the other important factor that we need to consider is patients who are younger and may have many different CLL treatments over the years. We have to be very careful, I think, about how we sequence these drugs. We know right now that we can start with covalent BTK inhibitors and then subsequently patients will respond well to the non-covalent inhibitor pirtobrutinib in later lines of therapy. But right now we do not have prospective data the other way around. So how will the patients on these studies who progress on pirtobrutinib respond to covalent BTK inhibitors? We do not know yet. There have not been a lot of progression events, which is great, but we would like to see some data in that respect to feel more comfortable with that sequence. Now, I do think that particularly for older patients and those who have significant cardiovascular comorbidities, if they wanted to go on a continuous BTK inhibitor, I do think these data really strongly support using pirtobrutinib as the BTK inhibitor of choice in that population. In particular, the cardiovascular risks with pirtobrutinib seem to be quite low. I was very struck in the comparison with BR that the rate of AFib was equivalent between the two arms of the study. And that is really the first time we have seen that with any of these BTK inhibitors, no elevated risk of AFib in a randomized study. I think that is the population where it will get the most traction first, is the upfront, sort of older patient with significant cardiovascular comorbidities. And as the data from these studies mature, I think that we will start to see more widespread use of pirtobrutinib in the frontline setting. Dr. Jonathan Friedberg: Jennifer, I am just curious if you have any personal experience or heard anecdotally about after progression on pirtobrutinib the use of other BTK inhibitors and whether there is a growing experience there. Dr. Jennifer Woyach: I do not think that there is much clinical experience, you know, as Matt alluded to, it certainly has not been tested yet. There has been some data in relapsed CLL suggesting that in people who have resistance mutations to covalent BTK inhibitors after treatment with pirtobrutinib, sometimes those mutations go away. I think most of us are concerned that they are probably not actually gone but maybe in compartments that we just have not sampled, suggesting that sort of approach where you might sequence a covalent inhibitor after a non-covalent in somebody who had already been resistant probably would not work that well. But, you know, in this setting where people had never been exposed to a covalent BTK inhibitor before, we really have no idea what the resistance patterns are going to be like. We assume they will be the same as what we have seen in relapsed CLL, but I think we just need some longer follow-up to know for sure. Dr. Wojciech Jurczak: If I may confront Dr. Davids about the use of covalent BTK inhibitors upfront, well, I think that we should abandon the idea of using the first and the second and the third generation, at least if we don't have medical lines. If we endlessly block the same pathway, it is not going to be effective. So if pirtobrutinib gets approval in first, second line, we do not necessarily have to use it in the first line. I am not here in a position to defend that we should treat patients with pirtobrutinib upfront and not BCL2 time-limited regimen. However, the way I look at CLL patients when choosing therapy is not just how should I treat them now, but what would be the best regimen in 5, 10 years if I have to re-treat them. And in some instances, the idea may be that in this setting we would like to have a BTK inhibitor upfront to have a BCL2 inhibitor later to make it time-limited. Although I understand and I agree with Matthew that if we have an elderly, fragile population, then the charm of having a drug taken once a day in a tablet with literally few cardiovascular adverse events might be an option. Dr. Jonathan Friedberg: And I will give Matt the last word whether he wants to respond to that, and also just as a forward-looking issue, I know both investigators have implied that there will be future studies looking at combinations with pirtobrutinib, and if you have any sense as to what you would be looking for there. Dr. Matthew Davids: The field really is heading toward time-limited therapy for most patients, I would say. There is a bit of a discrepancy right now in the field between sort of what we are doing in academic practice and what is done sort of more widely in community practice. And so right now we are going to see evolving datasets comparing these approaches. We are already seeing data now from the CLL17 study with ibrutinib comparing continuous to time-limited venetoclax-based therapy, and we are seeing similar efficacy benefits from these time-limited therapies without the need for continuous treatment. And so that is where I think some of the future studies with pirtobrutinib combining it with venetoclax and other partners are so important. Fortunately, several of these studies are already ongoing, including a phase 3 trial called CLL18, which is looking at pirtobrutinib with venetoclax, comparing that to venetoclax and obinutuzumab. So I am optimistic that we are going to be developing these very robust datasets where we can actually use pirtobrutinib in the frontline setting as a time-limited therapy as a component of a multi-drug regimen. So far, those early data are very promising. Dr. Wojciech Jurczak: Perhaps last but not least, in a single center we have treated over 300 patients with pirtobrutinib. So eventually some of them relapsed. And I must say that our experience on BCL2 inhibitors, not just venetoclax but including sonrotoclax, are appealingly good. Therefore, by using pirtobrutinib even earlier, we do not block the efficacy of other compounds. Dr. Jonathan Friedberg: All right. Well, I want to thank all of our speakers. I also want to congratulate our two guests who presented these very influential papers at the ASH Annual Meeting, and chose to publish them in JCO, so we thank you for that, and Dr. Davids for your commentary - really appreciated. That is this episode of JCO After Hours. Thank you for your attention. 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.   Disclosures Dr. Wojciech Jurczak Consulting or Advisory Role: BeiGene, Lilly, Abbvie/Genentech, Takeda, Roche, AstraZeneca Research Funding: Roche, Takeda, Janssen-Cilag, BeiGene, AstraZeneca, Lilly, Abbvie/Genentech Dr. Jennifer Woyach Consulting or Advisory Role: Pharmacyclics, Janssen, AstraZeneca, Beigene, Loxo, Newave Pharmaceutical, Genentech, Abbvie, Merck Research Funding: Company name: Janssen, Schrodinger, beone, Abbvie, Merck, Loxo/Lilly Dr. Matthew Davids Honoraria: Curio Science, Aptitude Health, Bio Ascend, PlatformQ Health, Plexus Consulting or Advisory Role: Genentech, Janssen, Abbvie, AstraZeneca, Adaptive Biotechnologies, Ascentage Pharma, BeiGene, Lilly, Bristol-Myers Squibb, Genmab, Merck, MEI Pharma, Nuvalent, Inc., Galapagos NV, Schroedinger Research Funding: Ascentage Pharma, Novartis, MEI Pharma, AstraZeneca  

Stay ahead in NSCLC management with this accredited podcast! HER2 alterations, including gene mutations and protein overexpression, are key therapeutic targets, but their complexity can challenge treatment decisions. In Module 1 of this podcast, Dr. Julia Kathleen Rotow, Clinical Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, provides essential insights and testing recommendations to optimize patient care. Listen now! Click here to claim CME/NCPD credit: bit.ly/49NCaQu

Stay ahead in NSCLC management with our accredited podccast! HER2 alterations, including gene amplifications, mutations, and protein overexpression, are critical therapeutic targets, but their heterogeneity can complicate treatment strategies. In Module 2, Dr. Julia Kathleen Rotow, Clinical Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, explores advanced testing methodologies and strategies to navigate HER2 complexities and optimize patient outcomes. Listen now! Click here to claim CME/NCPD credit: bit.ly/405xEJO

Patrick Y. Wen, MD, Dana-Farber Cancer Institute, Boston, MA, discusses current standards of care for low- and high-grade gliomas, including the importance of comprehensive molecular testing, the World Health Organization classification of tumors of the central nervous system, and newly available therapies. 

In today's episode, we had the pleasure of speaking with Jacob Sands, MD, and Shailee Shah, MD, about considerations for diagnosing and managing Lambert-Eaton myasthenic syndrome (LEMS), particularly in the context of small cell lung cancer (SCLC). Dr Sands is associate chief of the Lowe Center for Thoracic Oncology and the Oncology Medical Director of the International Patient Center at Dana-Farber Cancer Institute, as well as an assistant professor at Harvard Medical School in Boston, Massachusetts. Dr Shah is a clinical assistant professor of neurology (MS/neuroimmunology) at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.  In our exclusive interview, Drs Sands and Shah discussed LEMS symptom identification, the importance of paraneoplastic panels for assessing neurologic dysfunction in patients with SCLC, the need for specific autoantibody testing, and what guidelines currently note as best practices for the diagnosis of this disease. 

In this episode of the Oncology Brothers podcast, we took a deeper dive into the evolving landscape of CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Joined by esteemed oncologists Dr. Sara Tolaney from Dana-Farber Cancer Institute and Dr. Adam Brufsky from UPMC Hillman Cancer Center, the discussion focused on real-world scenarios involving adjuvant and metastatic settings. Key topics included: • The recent updates from the MonarchE and NATALEE trials, highlighting the approval of abemaciclib and ribociclib. • Strategies for selecting the right adjuvant treatment for high-risk patients, including dosing considerations and side effect management. • Insights into managing common toxicities associated with CDK4/6 inhibitors, such as diarrhea and QTc prolongation. • The role of CDK4/6 inhibitors in patients with visceral involvement and the implications of using these therapies in the metastatic setting. Whether you're a healthcare professional or someone interested in the latest advancements in breast cancer treatment, this episode provided valuable insights and expert opinions on navigating complex treatment decisions. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for more episodes and send us your challenging cases for future discussions! #CDK4/6i #BreastCancer #MonarchE #NATALEE #Abemaciclib #Ribociclib #OncologyBrothers #HRpositive

Authors Drs. Jessica Ross and Alissa Cooper share insights into their JCO PO article, "Clinical and Pathologic Landscapes of Delta-Like Ligand 3 and Seizure-Related Homolog Protein 6 Expression in Neuroendocrine Carcinomas"  Host Dr. Rafeh Naqash and Drs. Ross and Cooper discuss the landscape of Delta-like ligand 3 (DLL3) and seizure-related homolog protein 6 (SEZ6) across NECs from eight different primary sites. 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 PO and an Associate Professor at the OU Health Stephenson Cancer Center. Today, I'm excited to be joined by Dr. Jessica Ross, third-year medical oncology fellow at the Memorial Sloan Kettering Cancer Center, as well as Dr. Alissa Cooper, thoracic medical oncologist at the Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School. Both are first and last authors of the JCO Precision Oncology article entitled "Clinical and Pathologic Landscapes of Delta-like Ligand 3 and Seizure-Related Homolog Protein 6 or SEZ6 Protein Expression in Neuroendocrine Carcinomas." At the time of this recording, our guest disclosures will be linked in the transcript. Jessica and Alissa, welcome to our podcast, and thank you for joining us today. Dr. Jessica Ross: Thanks very much for having us. Dr. Alissa Cooper: Thank you. Excited to be here. Dr. Rafeh Naqash: It's interesting, a couple of days before I decided to choose this article, one of my GI oncology colleagues actually asked me two questions. He said, "Rafeh, do you know how you define DLL3 positivity? And what is the status of DLL3 positivity in GI cancers, GI neuroendocrine carcinomas?" The first thing I looked up was this JCO article from Martin Wermke. You might have seen it as well, on obrixtamig, a phase 1 study, a DLL3 bi-specific T-cell engager. And they had some definitions there, and then this article came along, and I was really excited that it kind of fell right in place of trying to understand the IHC landscape of two very interesting targets. Since we have a very broad and diverse audience, especially community oncologists, trainees, and of course academic clinicians and some people who are very interested in genomics, we'll try to make things easy to understand. So my first question for you, Jessica, is: what is DLL3 and SEZ6 and why are they important in neuroendocrine carcinomas? Dr. Jessica Ross: Yeah, good question. So, DLL3, or delta-like ligand 3, is a protein that is expressed preferentially on the tumor cell surface of neuroendocrine carcinomas as opposed to normal tissue. It is a downstream target of ASCL1, and it's involved in neuroendocrine differentiation, and it's an appealing drug target because it is preferentially expressed on tumor cell surfaces. And so, it's a protein, and there are several drugs in development targeting this protein, and then Tarlatamab is an approved bi-specific T-cell engager for the treatment of extensive-stage small cell lung cancer in the second line. SEZ6, or seizure-like homolog protein 6, is a protein also expressed on neuroendocrine carcinoma cell surface. Interestingly, so it's expressed on neuronal cells, but its exact role in neuroendocrine carcinomas and oncogenesis is actually pretty poorly understood, but it was identified as an appealing drug target because, similarly to DLL3, it's preferentially expressed on the tumor cell surface. And so this has also emerged as an appealing drug target, and there are drugs in development, including antibody-drug conjugates, targeting this protein for that reason. Dr. Alissa Cooper: Over the last 10 to 15 years or so, there's been an increasing focus on precision oncology, finding specific targets that actually drive the cancer to grow, not just within lung cancer but in multiple other primary cancers. But specifically, at least speaking from a thoracic oncology perspective, the field of non-small cell lung cancer has completely exploded over the past 15 years with the discovery of driver oncogenes and then matched targeted therapies. Within the field of neuroendocrine carcinomas, including small cell lung cancer but also other high-grade neuroendocrine carcinomas, there has not been the same sort of progress in terms of identifying targets with matched therapies. And up until recently, we've sort of been treating these neuroendocrine malignancies kind of as a monolithic disease process. And so recently, there's been sort of an explosion of research across the country and multiple laboratories, multiple people converging on the same open questions about why might patients with specific tumor biologies have different kind of responses to different therapies. And so first this came from, you know, why some patients might have a good response to chemo and immunotherapy, which is the first-line approved therapy for small cell lung cancer, and we also sort of extrapolate that to other high-grade neuroendocrine carcinomas. What's the characteristic of that tumor biology? And at the same time, what are other targets that might be identifiable? Just as Jesse was saying, they're expressed on the cell surface, they're not necessarily expressed in normal tissue. Might this be a strategy to sort of move forward and create smarter therapies for our patients and therefore move really into a personalized era for treatment for each patient? And that's really driving, I think, a lot of the synthesis of this work of not only the development of multiple new therapies, but really understanding which tumor might be the best fit for which therapy. Dr. Rafeh Naqash: Thank you for that explanation, Alissa. And as you mentioned, these are emerging targets, some more further along in the process with approved drugs, especially Tarlatamab. And obviously, DLL3 was something identified several years back, but drug development does take time, and readout for clinical trials takes time. Could you, for the sake of our audience, try to talk briefly about the excitement around Tarlatamab in small cell lung cancer, especially data that has led to the FDA approval in the last year, year and a half? Dr. Alissa Cooper: Sure. Yeah, it's really been an explosion of excitement over, as you're saying, the last couple of years, and work really led by our mentor, Charlie Rudin, had identified DLL3 as an exciting target for small cell lung cancer specifically but also potentially other high-grade neuroendocrine malignancies. Tarlatamab is a DLL3-targeting bi-specific T-cell engager, which targets DLL3 on the small cell lung cancer cells as well as CD3 on T cells. And the idea is to sort of introduce the cancer to the immune system, circumventing the need for MHC class antigen presentation, which that machinery is typically not functional in small cell lung cancer, and so really allowing for an immunomodulatory response, which had not really been possible for most patients with small cell lung cancer prior to this. Tarlatamab was tested in a phase 2 registrational trial of about 100 patients and demonstrated a response rate of 40%, which was very exciting, especially compared with other standard therapies which were available for small cell lung cancer, which are typically cytotoxic therapies. But most excitingly, more than even the response rate, I think, in our minds was the durability of response. So patients whose disease did have a response to Tarlatamab could potentially have a durable response lasting a number of months or even over a year, which had previously not ever been seen in this in the relapsed/refractory setting for these patients. I think the challenge with small cell lung cancer and other high-grade neuroendocrine malignancies is that a response to therapy might be a bit easier to achieve, but it's that durability. The patient's tumors really come roaring back quite aggressively pretty quickly. And so this was sort of the most exciting prospect is that durability of response, that long potential overall survival tail of the curve really being lifted up. And then most recently at ASCO this year, Dr. Rudin presented the phase 3 randomized controlled trial which compared Tarlatamab to physician's choice of chemotherapy in a global study. And the choice of chemotherapy did vary depending on the part of the world that the patients were enrolled in, but in general, it was a really markedly positive study for response rate, for progression-free survival, and for overall survival. Really exciting results which really cemented Tarlatamab's place as the standard second-line therapy for patients with small cell lung cancer whose disease has progressed on first-line chemo-immunotherapy. So that has been very exciting. This drug was FDA approved in May of 2024, and so has been used extensively since then. I think the adoption has been pretty widespread, at least in the US, but now in this global trial that was just presented, and there was a corresponding New England Journal paper, I think really confirms that this is something we really hopefully can offer to most of our patients. And I think, as we all know, that this therapy or other therapies like it are also being tested potentially in the first-line setting. So there was data presented with Tarlatamab incorporated into the maintenance setting, which also showed exciting results, albeit in a phase 1 trial, but longer overall survival than we're used to seeing in this patient population. And we await results of the study that is incorporating Tarlatamab into the induction phase with chemotherapy as well. So all of this is extraordinarily exciting for our patients to sort of move the needle of how many patients we can keep alive, feeling functional, feeling well, for as long as possible. Dr. Rafeh Naqash: Very exciting session at ASCO. I was luckily one of the co-chairs for the session that Dr. Rudin presented it, and I remember somebody mentioning there was more progress seen in that session for small cell lung cancer than the last 30, 35 years for small cell, very exciting space and time to be in as far as small cell lung cancer. Now going to this project, Jessica, since you're the first author and Alissa's the last, I'm assuming there was a background conversation that you had with Alissa before you embarked on this project as an idea. So could you, again, for other trainees who are interested in doing research, and it's never easy to do research as a resident and a fellow when you have certain added responsibilities. Could you give us a little bit of a background on how this started and why you wanted to look at this question? Dr. Jessica Ross: Yeah, sure. So, as with many exciting research concepts, I think a lot of them are derived from the clinic. And so I think Alissa and I both see a good number of patients with small cell, large cell lung cancer, and then high-grade neuroendocrine carcinomas. And so I think this was really born out of a basic conversation of we have these drugs in development targeting these two proteins, DLL3 and SEZ6, but really what is the landscape of cancers that express these proteins and who are the patients that really might benefit from these exciting new therapies. And of course, there was some data out there, but sort of less than one would imagine in terms of, you know, neuroendocrine carcinomas can really come from anywhere in the body. And so when you're seeing a patient with small cell of the cervix, for example, like what are the chances that their cancer expresses DLL3 or expresses SEZ6? So it was really derived from this pragmatic, clinically oriented question that we had both found ourselves thinking about, and we were lucky enough at MSK, we had started systematically staining patients' tumors for DLL3, tumors that are high-grade neuroendocrine carcinomas, and then we had also more recently started staining for SEZ6 as well. And so we had this nice prospectively collected dataset with which to answer this question. Dr. Rafeh Naqash: Excellent. And Alissa, could you try to go into some of the details around which patients you chose, how many patients, what was the approach that you selected to collect the data for this project? Dr. Alissa Cooper: This is perhaps a strength but also maybe a limitation of this dataset is, as Jesse alluded to, our pathology colleagues are really the stars of this paper here because we were lucky enough at MSK that they were really forethinking. They are absolute experts in the field and really forward-thinking people in terms of what information might be needed in the future to drive treatment decision-making. And so, as Jesse had said, small cell lung cancer tumor samples reflexively are stained for DLL3 and SEZ6 at MSK if there's enough tumor tissue. The other high-grade neuroendocrine carcinomas, those stains are performed upon physician request. And so that is a bit of a mixed bag in terms of the tumor samples we were able to include in this dataset because, you know, upon physician request depends on a number of factors, but actually at MSK, a number of physicians were requesting these stains to be done on their patients with high-grade neuroendocrine cancers of of other histologies. So we looked at all tumor samples with a diagnosis of high-grade neuroendocrine carcinoma of any histology that were stained for these two stains of interest. You know, I can let Jesse talk a bit more about the methodology. She was really the driver of this project. Dr. Jessica Ross: Yeah, sure. So we had 124 tumor samples total. All of those were stained for DLL3, and then a little less than half, 53, were stained for SEZ6. As Alissa said, they were from any primary site. So about half of them were of lung origin, that was the most common primary site, but we included GI tract, head and neck, GU, GYN, even a few tumors of unknown origin. And again, that's because I think a lot of these trials are basket trials that are including different high-grade neuroendocrine carcinomas no matter the primary site. And so we really felt like it was important to be more comprehensive and inclusive in this study. And then, methodologically, we also defined positivity in terms of staining of these two proteins as anything greater than or equal to 1% staining. There's really not a defined consensus of positivity when it comes to these two novel targets and staining for these two proteins. But in the Tarlatamab trials, for some of the correlative work that's been done, they use that 1% cutoff, and we just felt like being consistent with that and also using a sort of more pragmatic yes/no cutoff would be more helpful for this analysis. Dr. Alissa Cooper: And that was a point of discussion, actually. We had contemplated multiple different schemas, actually, for how to define thresholds of positivity. And I know you brought up that question before, what does it mean to be DLL3 positive or DLL3 high? I think you were alluding to prior that there was a presentation of obrixtamig looking at extra-pulmonary neuroendocrine carcinomas, and they actually divvied up the results between DLL3 50% or greater versus DLL3 low under 50%. And they actually did demonstrate differential efficacy certainly, but also some differential safety as well, which is very provocative and that kind of analysis has not been presented for other novel therapies as far as I'm aware. I could be wrong, but as far as I'm aware, that was sort of the first time that we saw a systematic presentation of considering patients to be, quote unquote, "high" or "low" in these sort of novel targets. I think it is important because the label for Tarlatamab does not require any DLL3 expression at all, actually. So it's not hinging upon DLL3 expression. They depend on the fact that the vast majority of small cell lung cancer tumors do express DLL3, 85% to 90% is what's been demonstrated in a few studies. And so, there's not prerequisite testing needed in that regard, but maybe for these extra-pulmonary, other histology neuroendocrine carcinomas, maybe it does matter to some degree. Dr. Rafeh Naqash: Definitely agree that this evolving landscape of trying to understand whether an expression for something actually really does correlate with, whether it's an immune cell engager or an antibody-drug conjugate is a very evolving and dynamically moving space. And one of the questions that I was discussing with one of my friends was whether IHC positivity and the level of IHC positivity, as you've shown in one of those plots where you have double positive here on the right upper corner, you have the double negative towards the left lower, whether that somehow determines mRNA expression for DLL3. Obviously, that was not the question here that you were looking at, but it does kind of bring into question certain other aspects of correlations, expression versus IHC. Now going to the figures in this manuscript, very nicely done figures, very easy to understand because I've done the podcast for quite a bit now, and usually what I try to do first is go through the figures before I read the text, and and a lot of times it's hard to understand the figures without reading the text, but in your case, specifically the figures were very, very well done. Could you give us an overview, a quick overview of some of the important results, Jessica, as far as what you've highlighted in the manuscript? Dr. Jessica Ross: Sure. So I think the key takeaway is that, of the tumors in our cohort, the majority were positive for DLL3 and positive for SEZ6. So about 80% of them were positive for DLL3 and 80% were positive for SEZ6. About half of the tumors were stained for both proteins, and about 65% of those were positive as well. So I think if there's sort of one major takeaway, it's that when you're seeing a patient with a high-grade neuroendocrine carcinoma, the odds are that their tumor will express both of these proteins. And so that can sort of get your head thinking about what therapies they might be eligible for. And then we also did an analysis of some populations of interest. So for example, we know that non-neuroendocrine pathologies can transform into neuroendocrine tumors. And so we specifically looked at that subset of patients with transformed tumors, and those were also- the majority of them were positive, about three-quarters of them were positive for both of these two proteins. We looked at patients with brain met samples, again, about 70% were positive. And then I'd say the last sort of population of interest was we had a subset of 10 patients who had serial biopsies stained for either DLL3 or SEZ6 or both. In between the two samples, these patients were treated with chemotherapy. They were not treated with targeted therapy, but interestingly, in the majority of cases, the testing results were concordant, meaning if it was DLL3 positive to begin with, it tended to remain DLL3 positive after treatment. And so I think that's important as well as we think about, you know, a patient who maybe had DLL3 testing done before they received their induction chemo-IO, we can somewhat confidently say that they're probably still DLL3 positive after that treatment. And then finally, we did do a survival analysis among specifically the patients with lung neuroendocrine carcinomas. We looked at whether DLL3 expression affected progression-free survival on first-line platinum-etoposide, and then we looked at did it affect overall survival. And we found that it did not have an impact or the median progression-free survival was similar whether you were DLL3 positive or negative. But interestingly, with overall survival, we found that DLL3 positivity actually correlated with slightly improved overall survival. These were small numbers, and so, you know, I think we have to interpret this with caution, for sure, but it is interesting. I think there may be something to the fact that five of the patients who were DLL3 positive were treated with DLL3-targeting treatments. And so this made me think of, like in the breast cancer world, for example, if you have a patient with HER2-positive disease, it initially portended worse prognosis, more aggressive disease biology, but on the other hand, it opens the door for targeted treatments that actually now, at least with HER2-positive breast cancer, are associated with improved outcomes. And so I think that's one finding of interest as well. Dr. Rafeh Naqash: Definitely proof-of-concept findings here that you guys have in the manuscript. Alissa, if I may ask you, what is the next important step for a project like this in your mind? Dr. Alissa Cooper: Jesse has highlighted a couple of key findings that we hope to move forward with future investigative studies, not necessarily in a real-world setting, but maybe even in clinical trial settings or in collaboration with sponsors. Are these biomarkers predictive? Are they prognostic? You know, those are still- we have some nascent data, data has been brewing, but I think that we we still don't have the answers to those open questions, which I think are critically important for determining not only clinical treatment decision-making, but also our ability to understand sequencing of therapies, prioritization of therapies. I think a prospective, forward-looking project, piggybacking on that paired biopsy, you know, we had a very small subset of patients with paired biopsies, but a larger subset or cohort looking at paired biopsies where we can see is there evolution of these IHC expression, even mRNA expression, as you're saying, is there differential there? Are there selection pressures to targeted therapies? Is there upregulation or downregulation of targets in response not just to chemotherapy, but for example, for other sort of ADCs or bi-specific T-cell engagers? I think those are going to be critically important future studies which are going to be a bit challenging to do, but really important to figure out this key clinical question of sequencing, which we're all contemplating in our clinics day in and day out. If you have a patient, and these patients often can be sick quite quickly, they might have one shot of what's the next treatment that you're going to pick. We can't guarantee that every patient is going to get to see every therapy. How can you help to sort of answer the question of like what should you offer? So I think that's the key question sort of underlying any future work is how predictive or prognostic are these biomarkers? What translational or correlative studies can we do on the tissue to understand clinical treatment decision-making? I think those are the key things that will unfold in the next couple of years. Dr. Rafeh Naqash: The last question for you, Alissa, that I have is, you are fairly early in your career, and you've accomplished quite a lot. One of the most important things that comes out from this manuscript is your mentorship for somebody who is a fellow and who led this project. For other junior investigators, early-career investigators, how did you do this? How did you manage to do this, and how did you mentor Jessica on this project with some of the lessons that you learned along the way, the good and other things that would perhaps help other listeners as they try to mentor residents, trainees, which is one of the important things of what we do in our daily routine? Dr. Alissa Cooper: I appreciate you calling me accomplished. Um, I'm not sure how true that is, but I appreciate that. I didn't have to do a whole lot with this project because Jesse is an extraordinarily smart, driven, talented fellow who came up with a lot of the clinical questions and a lot of the research questions as well. And so this project was definitely a collaborative project on both of our ends. But I think what was helpful from both of our perspectives is from my perspective, I could kind of see that this was a gap in the literature that really, I think, from my work leading clinical trials and from treating patients with these kinds of cancers that I really hoped to answer. And so when I came to Jessica with this idea as sort of a project to complete, she was very eager to take it and run with it and also make it her own. You know, in terms of early mentorship, I have to admit this was the first project that I mentored, so it was a great learning experience for me as well because as an early-career clinician and researcher, you're used to having someone else looking over your shoulder to tell you, "Yes, this is a good journal target, here's what we can anticipate reviewers are going to say, here are other key collaborators we should include." Those kind of things about a project that don't always occur to you as you're sort of first starting out. And so all of that experience for me to be identifying those more upper-level management sort of questions was a really good learning experience for me. And of course, I was fantastically lucky to have a partner in Jesse, who is just a rising star. Dr. Jessica Ross: Thank you. Dr. Rafeh Naqash: Well, excellent. It sounds like the first of many other mentorship opportunities to come for you, Alissa. And Jessica, congratulations on your next step of joining and being faculty, hopefully, where you're training. Thank you again, both of you. This was very insightful. I definitely learned a lot after I reviewed the manuscript and read the manuscript. Hopefully, our listeners will feel the same. Perhaps we'll have more of your work being published in JCO PO subsequently. Dr. Alissa Cooper: Hope so. Thank you very much for the opportunity to chat today. Dr. Jessica Ross: Yes, thank you. This was great. Dr. Rafeh Naqash: 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 as 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. Disclosures: Dr. Alissa Jamie Cooper Honoraria Company: MJH Life Scienes, Ideology Health, Intellisphere LLC, MedStar Health, Physician's Education Resource, LLC,  Gilead Sciences, Regeneron, Daiichi Sankyo/Astra Zeneca, Novartis,  Research Funding: Merck, Roche, Monte Rosa Therapeutics, Abbvie, Amgen, Daiichi Sankyo/Astra Zeneca Travel, Accommodations, Expenses: Gilead Sciences

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. In this inaugural episode, Dr Matulonis welcomed guest Taymaa May, MD, MSc, to discuss advances in gynecologic cancer surgery. Dr May is the director of Ovarian Cancer Surgery in the Division of Surgical Oncology at the Brigham and Women's Hospital in Boston, as well as an associate professor at Harvard Medical School. One of the biggest transformative changes in the field has been the introduction of minimally invasive surgery using laparoscopic and robotic platforms, Dr May emphasized. This allows for precise cancer staging surgery and faster patient recovery without compromising cancer outcomes, she noted. Complementing this has been the innovation of sentinel lymph node mapping, which uses technology, such as an infrared dye, to precisely identify and remove only the necessary lymph nodes. This offers equal staging precision and reduces patient morbidity with lower extremity lymphedema, a common adverse effect associated with older, extensive lymph node dissections, according to Dr May. The experts stressed the importance of consulting a gynecologic oncology surgeon, as national studies indicate that patients assessed and operated on by these specialists achieve the most optimal clinical outcomes. For advanced ovarian cancer, which often requires complex multivisceral resection to achieve optimal tumor removal, Dr May explained that surgical innovations are used to enhance recovery. For example, she noted that fluorescence angiography assesses blood flow in fresh bowel sutures intraoperatively, which helps ensure proper healing and minimizes complications. In cervical cancer, Dr May said that radical trachelectomy offers a safe, fertility-preserving option for young patients with suitable tumors. Furthermore, when determining treatment for patients with advanced ovarian cancer, she emphasized that personalization is key. Ultimately, Drs Matulonis and May reported that integrating surgical innovation into gynecologic cancer treatment protocols ensures optimal recovery, which is critical for patients to start subsequent treatments, like chemotherapy, on time.

How This Is Building Me, hosted by world-renowned oncologist D. Ross Camidge, MD, PhD, is a podcast focused on the highs and lows, ups and downs of all those involved with cancer, cancer medicine, and cancer science across the full spectrum of life's experiences. In this episode, Dr Camidge sat down with Mark Socinski, MD, a medical oncologist and the executive medical director of the AdventHealth Cancer Institute in Orlando, Florida. Drs Camidge and Socinski discussed the highlights of Dr Socinski's career trajectory, as well as the personal influences that helped him arrive where he is today. Socinski describes himself as a clinician and clinical investigator with 35 years of focus on lung cancer. His role as executive director of the AdventHealth Cancer Institute involves maintaining an active clinic 1 day a week and dedicating the rest of his time to administrative duties, including recruitment and building infrastructure at the institution. In the interview, Dr Socinski explained that he was influenced to enter a career in medicine because of role of the family practitioner he knew growing up. He went on to receive undergraduate and medical degrees from the University of Vermont in Burlington. After training at Dana-Farber Cancer Institute in Boston, Massachusetts, he began his career in private general oncology practice in Vermont before seeking a more academic, subspecialty environment. He joined the University of North Carolina to concentrate on lung cancer, where he pioneered dose-escalation trials using conformal radiotherapy. Dr Socinski then described his move to the University of Pittsburgh Medical Center in Pennsylvania. There, he became the chair of the lung pathway, which limits treatment options to a single, expert-agreed standard of care based on efficacy, toxicity, and cost, thus reducing treatment heterogeneity and controlling costs. Thereafter, Dr Socinski moved to AdventHealth, attracted by the institution's goal to achieve National Cancer Institute designation and build a major cancer program. Dr Socinski shared that he finds it gratifying to care for patients and lead the development of the institute.

This Veterans Day, we're shining a light on care for those who've served.Dr. Elizabeth (Betsy) O'Donnell, Director of the Multi-Cancer Early Detection Clinic at Dana-Farber Cancer Institute, joins the PQI Podcast to discuss the Sentinel Study—a Department of Defense–sponsored clinical trial offering multi-cancer early detection (MCED) testing to U.S. veterans.Through a single blood draw, the test can screen for more than 50 types of cancer, addressing the urgent need for improved screening among veterans, who face a cancer risk nearly 20% higher than the general population.Dr. O'Donnell shares how this innovative study combines science, service, and compassion to bring life-saving research to those who've served—and what it could mean for the future of oncology care.Listen to learn more about:How early detection technology is transforming the future of cancer careWhy veterans face unique cancer risks linked to their serviceWhat makes the Sentinel Study a model for accessible, equitable screeningThe personal motivation that drives Dr. O'Donnell's workFor more information on the Sentinel study or to determine eligibility, visit redcap.link/VeteransScreeningStudy or contact the Sentinel Team at dfciprevention@mgb.org

Listen to JCO's Art of Oncology article, "The Man at the Bow" by Dr. Alexis Drutchas, who is a palliative care physician at Dana Farber Cancer Institute. The article is followed by an interview with Drutchas and host Dr. Mikkael Sekeres. Dr. Drutchas shares the deep connection she had with a patient, a former barge captain, who often sailed the same route that her family's shipping container did when they moved overseas many times while she was growing up. She reflects on the nature of loss and dignity, and how oncologists might hold patients' humanity with more tenderness and care, especially at the end of life. TRANSCRIPT Narrator: The Man at the Bow, by Alexis Drutchas, MD  It was the kind of day that almost seemed made up—a clear, cerulean sky with sunlight bouncing off the gold dome of the State House. The contrast between this view and the drab hospital walls as I walked into my patient's room was jarring. My patient, whom I will call Suresh, sat in a recliner by the window. His lymphoma had relapsed, and palliative care was consulted to help with symptom management. The first thing I remember is that despite the havoc cancer had wreaked—sunken temples and a hospital gown slipping off his chest—Suresh had a warm, peaceful quality about him. Our conversation began with a discussion about his pain. Suresh told me how his bones ached and how his fatigue left him feeling hollow—a fraction of his former self. The way this drastic change in his physicality affected his sense of identity was palpable. There was loss, even if it was unspoken. After establishing a plan to help with his symptoms, I pivoted and asked Suresh how he used to spend his days. His face immediately lit up. He had been a barge captain—a dangerous and thrilling profession that took him across international waters to transport goods. Suresh's eyes glistened as he described his joy at sea. I was completely enraptured. He shared stories about mornings when he stood alone on the bow, feeling the salted breeze as the barge moved through Atlantic waves. He spoke of calm nights on the deck, looking at the stars through stunning darkness. He traveled all over the globe and witnessed Earth's topography from a perspective most of us will never see. The freedom Suresh exuded was profound. He loved these voyages so much that one summer, despite the hazards, he brought his wife and son to experience the journey with him. Having spent many years of my childhood living in Japan and Hong Kong, my family's entire home—every bed, sheet, towel, and kitchen utensil—was packed up and crossed the Atlantic on cargo ships four times. Maybe Suresh had captained one, I thought. Every winter, we hosted US Navy sailors docked in Hong Kong for the holidays. I have such fond memories of everyone going around the table and sharing stories of their adventures—who saw or ate what and where. I loved those times: the wild abandon of travel, the freedom of being somewhere new, and the way identity can shift and expand as experiences grow. When Suresh shared stories of the ocean, I was back there too, holding the multitude of my identity alongside him. I asked Suresh to tell me more about his voyages: what was it like to be out in severe weather, to ride over enormous swells? Did he ever get seasick, and did his crew always get along? But Suresh did not want to swim into these perilous stories with me. Although he worked a difficult and physically taxing job, this is not what he wanted to focus on. Instead, he always came back to the beauty and vitality he felt at sea—what it was like to stare out at the vastness of the open ocean. He often closed his eyes and motioned with his hands as he spoke as if he was not confined to these hospital walls. Instead, he was swaying on the water feeling the lightness of physical freedom, and the way a body can move with such ease that it is barely perceptible, like water flowing over sand. The resonances of Suresh's stories contained both the power and challenges laden in this work. Although I sat at his bedside, healthy, my body too contained memories of freedom that in all likelihood will one day dissipate with age or illness. The question of how I will be seen, compared to how I hoped to be seen, lingered in my mind. Years ago, before going to medical school, I moved to Vail, Colorado. I worked four different jobs just to make ends meet, but making it work meant that on my days off, I was only a chairlift ride away from Vail's backcountry. I have a picture of this vigor in my mind—my snowboard carving into fresh powder, the utter silence of the wilderness at that altitude, and the way it felt to graze the powdery snow against my glove. My face was windburned, and my body was sore, but my heart had never felt so buoyant. While talking with Suresh, I could so vividly picture him as the robust man he once was, standing tall on the bow of his ship. I could feel the freedom and joy he described—it echoed in my own body. In that moment, the full weight of what Suresh had lost hit me as forcefully as a cresting wave—not just the physical decline, but the profound shift in his identity. What is more, we all live, myself included, so precariously at this threshold. In this work, it is impossible not to wonder: what will it be like when it is me? Will I be seen as someone who has lived a full life, who explored and adventured, or will my personhood be whittled down to my illness? How can I hold these questions and not be swallowed by them? "I know who you are now is not the person you've been," I said to Suresh. With that, he reached out for my hand and started to cry. We looked at each other with a new understanding. I saw Suresh—not just as a frail patient but as someone who lived a full life. As someone strong enough to cross the Atlantic for decades. In that moment, I was reminded of the Polish poet, Wislawa Szymborska's words, "As far as you've come, can't be undone." This, I believe, is what it means to honor the dignity of our patients, to reflect back the person they are despite or alongside their illness…all of their parts that can't be undone. Sometimes, this occurs because we see our own personhood reflected in theirs and theirs in ours. Sometimes, to protect ourselves, we shield ourselves from this echo. Other times, this resonance becomes the most beautiful and meaningful part of our work. It has been years now since I took care of Suresh. When the weather is nice, my wife and I like to take our young son to the harbor in South Boston to watch the planes take off and the barges leave the shore, loaded with colorful metal containers. We usually pack a picnic and sit in the trunk as enormous planes fly overhead and tugboats work to bring large ships out to the open water. Once, as a container ship was leaving the port, we waved so furiously at those working on board that they all started to wave back, and the captain honked the ships booming horn. Every single time we are there, I think of Suresh, and I picture him sailing out on thewaves—as free as he will ever be. Mikkael Sekeres: Welcome back to JCO's Cancer Stories: The Art of Oncology. This ASCO podcast features intimate narratives and perspectives from authors exploring their experiences in oncology. I'm your host, Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. What a treat we have today. We're joined by Dr. Alexis Drutchas, a Palliative Care Physician and the Director of the Core Communication Program at the Dana-Farber Cancer Institute, and Assistant Professor of Medicine at Harvard Medical School to discuss her article, "The Man at the Bow." Alexis, thank you so much for contributing to Journal of Clinical Oncology and for joining us to discuss your article. Dr. Alexis Drutchas: Thank you. I'm thrilled and excited to be here. Mikkael Sekeres: I wonder if we can start by asking you about yourself. Where are you from, and can you walk us a bit through your career? Dr. Alexis Drutchas: The easiest way to say it would be that I'm from the Detroit area. My dad worked in automotive car parts and so we moved around a lot when I was growing up. I was born in Michigan, then we moved to Japan, then back to Michigan, then to Hong Kong, then back to Michigan. Then I spent my undergrad years in Wisconsin and moved out to Colorado to teach snowboarding before medical school, and then ended up back in Michigan for that, and then on the east coast at Brown for my family medicine training, and then in Boston for work and training. So, I definitely have a more global experience in my background, but also very Midwestern at heart as well. In terms of my professional career trajectory, I trained in family medicine because I really loved taking care of the whole person. I love taking care of kids and adults, and I loved OB, and at the time I felt like it was impossible to choose which one I wanted to pursue the most, and so family medicine was a great fit. And at the core of that, there's just so much advocacy and social justice work, especially in the community health centers where many family medicine residents train. During that time, I got very interested in LGBTQ healthcare and founded the Rhode Island Trans Health Conference, which led me to work as a PCP at Fenway Health in Boston after that. And so I worked there for many years. And then through a course of being a hospitalist at BI during that work, I worked with many patients with serious illness, making decisions about discontinuing dialysis, about pursuing hospice care in the setting of ILD. I also had a significant amount of family illness and started to recognize this underlying interest I had always had in palliative care, but I think was a bit scared to pursue. But those really kind of tipped me over to say I really wanted to access a different level of communication skills and be able to really go into depth with patients in a way I just didn't feel like I had the language for. And so I applied to the Harvard Palliative Care Fellowship and luckily and with so much gratitude got in years ago, and so trained in palliative care and stayed at MGH after that. So my Dana-Farber position is newer for me and I'm very excited about it. Mikkael Sekeres: Sounds like you've had an amazing career already and you're just getting started on it. I grew up in tiny little Rhode Island and, you know, we would joke you have to pack an overnight bag if you travel more than 45 minutes. So, our boundaries were much tighter than yours. What was it like growing up where you're going from the Midwest to Asia, back to the Midwest, you wind up settling on the east coast? You must have an incredible worldly view on how people live and how they view their health. Dr. Alexis Drutchas: I think you just named much of the sides of it. I think I realize now, in looking back, that in many ways it was living two lives, because at the time it was rare from where we lived in the Detroit area in terms of the other kids around us to move overseas. And so it really did feel like that part of me and my family that during the summers we would have home leave tickets and my parents would often turn them in to just travel since we didn't really have a home base to come back to. And so it did give me an incredible global perspective and a sense of all the ways in which people develop community, access healthcare, and live. And then coming back to the Midwest, not to say that it's not cosmopolitan or diverse in its own way, but it was very different, especially in the 80s and 90s to come back to the Midwest. So it did feel like I carried these two lenses in the world, and it's been incredibly meaningful over time to meet other friends and adults and patients who have lived these other lives as well. I think for me those are some of my most connecting friendships and experiences with patients for people who have had a similar experience in living with sort of a duality in their everyday lives with that. Mikkael Sekeres: You know, you write about the main character of your essay, Suresh, who's a barge captain, and you mention in the essay that your family crossed the Atlantic on cargo ships four times when you were growing up. What was that experience like? How much of it do you remember? Dr. Alexis Drutchas: Our house, like our things, crossed the Atlantic four times on barge ships such as his. We didn't, I mean we crossed on airplanes. Mikkael Sekeres: Oh, okay, okay. Dr. Alexis Drutchas: We flew over many times, but every single thing we owned got packed up into containers on large trucks in our house and were brought over to ports to be sent over. So, I'm not sure how they do it now, but at the time that's sort of how we moved, and we would often go live in a hotel or a furnished apartment for the month's wait of all of our house to get there, which felt also like a surreal experience in that, you know, you're in a totally different country and then have these creature comforts of your bedroom back in Metro Detroit. And I remember thinking a lot about who was crossing over with all of that stuff and where was it going, and who else was moving, and that was pretty incredible. And when I met Suresh, just thinking about the fact that at some point our home could have been on his ship was a really fun connection in my mind to make, just given where he always traveled in his work. Mikkael Sekeres: It's really neat. I remember when we moved from the east coast also to the Midwest, I was in Cleveland for 18 years. The very first thing we did was mark which of the boxes had the kids' toys in it, because that of course was the first one we let them close it up and then we let them open it as soon as we arrived. Did your family do something like that as well so that you can, you know, immediately feel an attachment to your stuff when they arrived? Dr. Alexis Drutchas: Yeah, I remember what felt most important to our mom was our bedrooms. I don't remember the toys. I remember sort of our comforters and our pillowcases and things like that, yeah, being opened and it feeling really settling to think, "Okay, you know, we're in a completely different place and country away from most everything we know, but our bedroom is the same." That always felt like a really important point that she made to make home feel like home again in a new place. Mikkael Sekeres: Yeah, yeah. One of the sentences you wrote in your essay really caught my eye. You wrote about when you were younger and say, "I loved those times, the wild abandon of travel, the freedom of being somewhere new, the way identity can shift and expand as experiences grow." It's a lovely sentiment. Do you think those are emotions that we experience only as children, or can they continue through adulthood? And if they can, how do we make that happen, that sense of excitement and experience? Dr. Alexis Drutchas: I think that's such a good question and one I honestly think about a lot. I think that we can access those all the time. There's something about the newness of travel and moving, you know, I have a 3-year-old right now, and so I think many parents would connect to that sense that there is wonderment around being with someone experiencing something for the first time. Even watching my son, Oliver, see a plane take off for the first time felt joyous in a completely new way, that even makes me smile a lot now. But I think what is such a great connection here is when something is new, our eyes are so open to it. You know, we're constantly witnessing and observing and are excited about that. And I think the connection that I've realized is important for me in my work and also in just life in general to hold on to that wonderment is that idea of sort of witnessing or having a writer's eye, many would call it, in that you're keeping your eye open for the small beautiful things. Often with travel, you might be eating ramen. It might not be the first time you're eating it, but you're eating it for the first time in Tokyo, and it's the first time you've had this particular ingredient on it, and then you remember that. But there's something that we're attuned to in those moments, like the difference or the taste, that makes it special and we hold on to it. And I think about that a lot as a writer, but also in patient care and having my son with my wife, it's what are the special small moments to hold on to and allowing them to be new and beautiful, even if they're not as large as moving across the country or flying to Rome or whichever. I think there are ways that that excitement can still be alive if we attune ourselves to some of the more beautiful small moments around us. Mikkael Sekeres: And how do we do that as doctors? We're trained to go into a room and there's almost a formula for how we approach patients. But how do you open your mind in that way to that sense of wonderment and discovery with the person you're sitting across from, and it doesn't necessarily have to be medical? One of the true treats of what we do is we get to meet people from all backgrounds and all walks of life, and we have the opportunity to explore their lives as part of our interaction. Dr. Alexis Drutchas: Yeah, I think that is such a great question. And I would love to hear your thoughts on this too. I think for me in that sentence that you mentioned, sitting at that table with sort of people in the Navy from all over the world, I was that person to them in the room, too. There was some identity there that I brought to the table that was different than just being a kid in school or something like that. To answer your question, I wonder if so much of the challenge is actually allowing ourselves to bring ourselves into the room, because so much of the formula is, you know, we have these white coats on, we have learners, we want to do it right, we want to give excellent care. There's there's so many sort of guards I think that we put up to make sure that we're asking the right questions, we don't want to miss anything, we don't want to say the wrong thing, and all of that is true. And at the same time, I find that when I actually allow myself into the room, that is when it is the most special. And that doesn't mean that there's complete countertransference or it's so permeable that it's not in service of the patient. It just means that I think when we allow bits of our own selves to come in, it really does allow for new connections to form, and then we are able to learn about our patients more, too. With every patient, I think often we're called in for goals of care or symptom management, and of course I prioritize that, but when I can, I usually just try to ask a more open-ended question, like, "Tell me about life before you came to the hospital or before you were diagnosed. What do you love to do? What did you do for work?" Or if it's someone's family member who is ill, I'll ask the kids or family in the room, "Like, what kind of mom was she? You know, what special memory you had?" Just, I get really curious when there's time to really understand the person. And I know that that's not at all new language. Of course, we're always trying to understand the person, but I just often think understanding them is couched within their illness. And I'm often very curious about how we can just get to know them as people, and how humanizing ourselves to them helps humanize them to us, and that back and forth I think is like really lovely and wonderful and allows things to come up that were totally unexpected, and those are usually the special moments that you come home with and want to tell your family about or want to process and think about. What about you? How do you think about that question? Mikkael Sekeres: Well, it's interesting you ask. I like to do projects around the house. I hate to say this out loud because of course one day I'll do something terrible and everyone will remember this podcast, but I fancy myself an amateur electrician and plumber and carpenter and do these sorts of projects. So I go into interactions with patients wanting to learn about their lives and how they live their lives to see what I can pick up on as well, how I can take something out of that interaction and actually use it practically. My father-in-law has this phrase he always says to me when a worker comes to your house, he goes, he says to me, "Remember to steal with your eyes." Right? Watch what they do, learn how they fix something so you can fix it yourself and you don't have to call them next time. So, for me it's kind of fun to hear how people have lived their lives both within their professions, and when I practiced medicine in Cleveland, there were a lot of farmers and factory workers I saw. So I learned a lot about how things are made. But also about how they interact with their families, and I've learned a lot from people I've seen who were just terrific dads and terrific moms or siblings or spouses. And I've tried to take those nuggets away from those interactions. But I think you can only do it if you open yourself up and also allow yourself to see that person's humanity. And I wonder if I can quote you to you again from your essay. There's another part that I just loved, and it's about how you write about how a person's identity changes when they become a patient. You write, "And in that moment the full weight of what he had lost hit me as forcefully as a cresting wave. Not just the physical decline, but the profound shift in identity. What is more, we all live, me included, so precariously at this threshold. In this work, it's impossible not to wonder, what will it be like when it's me? Will I be seen as someone who's lived many lives, or whittled down only to someone who's sick?" Can you talk a little bit more about that? Have you been a patient whose identity has changed without asking you to reveal too much? Or what about your identity as a doctor? Is that something we have to undo a little bit when we walk in the room with the stethoscope or wearing a white coat? Dr. Alexis Drutchas: That was really powerful to hear you read that back to me. So, thank you. Yeah, I think my answer here can't be separated from the illness I faced with my family. And I think this unanimously filters into the way in which I see every patient because I really do think about the patient's dignity and the way medicine generally, not always, really does strip them of that and makes them the patient. Even the way we write about "the patient said this," "the patient said that," "the patient refused." So I generally very much try to have a one-liner like, "Suresh is a X-year-old man who's a barge captain from X, Y, and Z and is a loving father with a," you know, "period. He comes to the hospital with X, Y, and Z." So I always try to do that and humanize patients. I always try to write their name rather than just "patient." I can't separate that out from my experience with my family. My sister six years ago now went into sudden heart failure after having a spontaneous coronary artery dissection, and so immediately within minutes she was in the cath lab at 35 years old, coding three times and came out sort of with an Impella and intubated, and very much, you know, all of a sudden went from my sister who had just been traveling in Mexico to a patient in the CCU. And I remember desperately wanting her team to see who she was, like see the person that we loved, that was fighting for her life, see how much her life meant to us. And that's not to say that they weren't giving her great care, but there was something so important to me in wanting them to see how much we wanted her to live, you know, and who she was. It felt like there's some important core to me there. We brought pictures in, we talked about what she was living for. It felt really important. And I can't separate that out from the way in which I see patients now or I feel in my own way in a certain way what it is to lose yourself, to lose the ability to be a Captain of the ship, to lose the ability to do electric work around the house. So much of our identity is wrapped up in our professions and our craft. And I think for me that has really become forefront in the work of palliative care and in and in the teaching I do and in the writing I do is how to really bring them forefront and not feel like in doing that we're losing our ability to remain objective or solid in our own professional identities as clinicians and physicians. Mikkael Sekeres: Well, I think that's a beautiful place to end here. I can only imagine what an outstanding physician and caregiver you are also based on your writing and how you speak about it. You just genuinely come across as caring about your patients and your family and the people you have interactions with and getting to know them as people. It has been again such a treat to have Dr. Alexis Drutchas here. She is Director of the Core Communication Program at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School to discuss her article, "The Man at the Bow." Alexis, thank you so much for joining us. Dr. Alexis Drutchas: Thank you. This has been a real joy. Mikkael Sekeres: If you've enjoyed this episode, consider sharing it with a friend or colleague, or leave us a review. Your feedback and support helps us continue to save these important conversations. If you're looking for more episodes and context, follow our show on Apple, Spotify, or wherever you listen, and explore more from ASCO at ASCO.org/podcasts. Until next time, this has been Mikkael Sekeres for the ASCO podcast Cancer Stories: The Art 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. Show notes: Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr. Alexis Drutchas is a palliative care physician at Dana Farber Cancer Institute.

Show Notes: Eugene Kim shares his post-graduation journey staying in Boston to finish research at the Dana-Farber Cancer Institute which was part of his thesis and also laid down the groundwork for his own cancer research which he has conducted over the years. He credits his understanding of science to his time at Harvard.  He also worked at the now-closed Love the Border Cafe. Eugene reflects on the valuable lessons learned from working at the cafe and describes the unique subculture of the cafe's staff, including the Brazilian kitchen staff and the diverse backgrounds of the waiters and waitresses. Securing a Position in Research Eugene talks about his major in biochemical sciences and his interest in molecular biology. He describes how he got involved in research at the Dana-Farber Cancer Institute, working with a researcher named Sam Speck. Eugene details the hands-on experience he gained, including growing bacteria, running gels, and learning the importance of meticulous work, and shares memorable experiences of working there, including  biking through snow to continue his research during a Thanksgiving blizzard. Enrolling in Columbia Medical School Eugene discusses his decision to attend Columbia Medical School in New York City, influenced by his desire to learn in a bustling city and study at a school that was his top choice. Eugene talks about his four years in medical school, his  general surgical training, and working in a cancer research laboratory and developing an interest in pediatric cancer. Eugene recounts his experience during 9/11, including the hospital's response and his involvement in helping first responders at Ground Zero. He reflects on the impact of 9/11 on the New York City community and the long-term health effects on residents. A Focus on Pediatric Surgery Eugene explains his transition from adult surgery to pediatric surgery, driven by his desire to help children. He describes his training at Cincinnati Children's Hospital and the competitive nature of obtaining a spot in pediatric surgery training. Eugene shares his experience in Houston, Texas, and the importance of mentorship in his career. He discusses the challenges and rewards of being a pediatric surgeon, including the need to specialize in various areas of surgery. Eugene emphasizes the importance of mentorship in his career and his efforts to mentor young surgeons and researchers. He describes the physical and mental demands of long surgeries and the importance of staying physically fit. Eugene discusses the impact of new technologies on pediatric surgery, such as robotic surgery and advanced imaging techniques. He reflects on the importance of remaining open-minded to new technologies and incorporating them into his practice.  Harvard Reflections Eugene reflects on his time at Harvard, including his interest in art history and Japanese art and history taught by John Rosenfield. He shares his appreciation for the seminar course with Mark Ptashne, which deepened his interest in molecular biology. He also mentions an Introduction to Architecture course with James Ackerman.  Eugene discusses the importance of taking courses outside of his major and the impact of these courses on his career. He reflects on the value of the requirements at Harvard and how they broadened his perspective and knowledge. A Journey into Wine Eugene shares his interest in wine, including his extensive collection and the impact of the Palisades fire on his collection. He describes his journey into wine, including learning about different regions and types of wine. Eugene recounts a memorable experience of tasting rare wines with the head red wine maker from Penfolds in Australia. He reflects on the importance of balancing professional and personal interests and the joy of sharing his passion for wine with others. Timestamps: 04:44: Early Research Experience at Harvard 08:13: Medical School and Early Career  18:46: Transition to Pediatric Surgery  40:09: Mentorship and Professional Development 44:03: Personal Interests and Hobbies  51:03: Reflections on Harvard and Beyond  Links: Hospital website: https://researchers.cedars-sinai.edu/Eugene.KimX/about Twitter / X: https://x.com/dreskim LinkedIn: https://www.linkedin.com/in/eugenekim3/    

Thursday we were joined in studio by Mike and Karen Donnell. Mike is a coaching legend in New Hampshire and most recently, his Pembroke Academy Boys Basketball team won the NHIAA Division 2 championship in March at the Lundholm Gym in Durham. Last week Coach Donnell resigned his post at Pembroke Academy as he experienced a period of feeling tired and lacking the energy of which he's always had plenty. Later that day he received a call from the Dana Farber Cancer Institute informing him that cancer had returned to his liver and lungs. He now will be going for biopsies. His wife, Karen, a cancer survivor, has been his “rock” through this journey and a tremendous source of support for Mike throughout the years in their many endeavors and adventures.

As part of the European Society for Medical Oncology (ESMO) Congress 2025, CancerNetwork® spoke with a variety of experts about key takeaways from different late-breaking abstracts, oral presentations, and other sessions focused on potential advancements across cancer care. Presenting investigators highlighted updated results from clinical trials evaluating novel therapeutic strategies across different cancer populations, including breast cancer and lung cancer.  Phase 3 VIKTORIA-1 Trial Sara A. Hurvitz, MD, FACP, the Smith Family Endowed Chair in Women's Health and senior vice president and director of the Clinical Research Division at the Fred Hutch Cancer Center, and tumor chair in breast oncology for the ONCOLOGY® editorial advisory board, first discussed findings from the phase 3 VIKTORIA-1 trial (NCT05501886). Her presentation highlighted how VIKTORIA-1 was “the first study to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival [PFS] with PAM inhibition” for patients with PIK3CA wild-type advanced breast cancer. Data from the trial showed that gedatolisib plus fulvestrant (Faslodex) and palbociclib (Ibrance) produced a median PFS of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P

In this episode of the Oncology Brothers podcast, we dive into the groundbreaking data presented at ESMO 2025, focusing on the GU landscape, particularly prostate and bladder cancer. Join us as we welcome Dr. Stephanie Berg, a GU medical oncologist from the Dana-Farber Cancer Institute, to discuss key studies and their implications for patient care. Episode Highlights: ⁠PSMAddition: Explore the benefits of lutetium PSMA in metastatic hormone-sensitive prostate cancer, including improved radiographic progression-free survival when combined with ADT and ARPIs. Capitello-281: Highlights the use of Capivasertib in patients with PTEN loss, showing significant improvements in radiographic PFS. Potomac: Examining the role of durvalumab + BCG in high-risk non-muscle invasive bladder cancer, and the promising results from the Keynote 905 study involving enfortumab and pembrolizumab. IMVigor011: Delved into showcasing how ctDNA-guided therapy with atezolizumab can improve survival outcomes. Stay tuned as we navigate the complexities of treatment options, side effects, and the importance of patient-centered decision-making in oncology.  Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for more insights on treatment algorithms, FDA approvals, and conference highlights! #ESMO2025 #GUOncology #LutetiumPSMA #Enfortumab #BladderCancer #ProstateCancer #OncologyBrothers

In this episode of The HemOnc Pulse, host Melissa speaks with Omar Nadeem, MD, Senior Physician at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, about emerging genomic insights in smoldering multiple myeloma. The discussion focuses on recent research showing how molecular profiling can improve understanding of disease progression and refine risk stratification beyond traditional clinical models. Dr. Nadeem highlights how genomic data may help distinguish patients with smoldering myeloma who are at higher risk of progression from those likely to remain stable, offering the potential to guide more personalized treatment decisions. The conversation also explores the evolving landscape of precursor plasma cell disorders and the role of immunotherapy, including CAR T-cell therapy, in clinical management.      

Eric Fischer, a professor at Dana-Farber Cancer Institute, on creating a new class medicines -- targeted protein degraders.

JCO PO author Dr. Asaf Maoz at Dana-Farber Cancer Institute shares insights into article, “Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era.” Host Dr. Rafeh Naqash and Dr. Maoz discuss the causes of death in individuals with LS and the evolving role of immunotherapy. 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 Associate Professor Medicine, at the OU Health Stephenson Cancer Center. Today, I'm super thrilled to be joined by Dr. Asaf Maoz, Medical Oncologist at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and faculty at the Harvard Medical School, and also lead author on the JCO Precision Oncology article entitled "Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era." This publication will be a concurrent publication with an oral presentation at the annual CGA meeting. At the time of this recording, our guest's disclosures will be linked in the transcript. Asaf, I'm excited to welcome you on this podcast. Thank you for joining us today. Dr. Asaf Maoz: Thank you so much for highlighting our paper. Dr. Rafeh Naqash: Absolutely. And I was just talking to you that we met several years back when you were a trainee, and it looks like you've worked a lot in this field now, and it's very exciting to see that you consider JCOPO as a relevant home for some of your work. And the topic that you have published on is of significant interest to trainees from a precision medicine standpoint, to oncologists in general, covers a lot of aspects of immunotherapy. So, I'm really excited to talk to you about all of this. Dr. Asaf Maoz: Me too, me too. And yeah, I think JCOPO has great content in the area of cancer genetics and has done a lot to disseminate the knowledge in that area. Dr. Rafeh Naqash: Wonderful. So, let's get started and start off, given that we have hosts of different kinds of individuals who listen to this podcast, especially when driving from home to work or back, for the sake of making everything simple, can we start by asking you what is Lynch syndrome? How is it diagnosed? What are some of the main things to consider when you're trying to talk an individual where you suspect Lynch syndrome? Dr. Asaf Maoz: Lynch syndrome is an inherited predisposition to cancer, and it is common. So, we used to think that, or there's a general notion in the medical community that it is a rare condition, but we actually know now from multiple studies, including studies that look at the general population and do genetic testing regardless of any clinical phenotype, that Lynch syndrome is found in about 1 in 300 people in the general population. If you think about it in the United States, that means that there are over a million people living with Lynch syndrome in the United States. Unfortunately, most individuals with Lynch syndrome don't know they have Lynch syndrome at the current time, and that's where a lot of the efforts in the community are being made to help detect more individuals who have Lynch syndrome. Lynch syndrome is caused by pathogenic germline variants in mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, or as a result of pathogenic variants in EPCAM that cause silencing of the MSH2 gene. Dr. Rafeh Naqash: Excellent. Thank you for that explanation. Now, one of the other things I also realized, similar to BRCA germline mutations, where you require a second hit for individuals with Lynch syndrome to have mismatch repair deficient cancers, you also require a second hit to have that second hit result in an MSI-high cancer. Could you help us understand the difference of these two concepts where generally Lynch syndrome is thought of to be cancers that are mismatch repair deficient, but that's not necessarily true for all cases as we see in your paper. Can you tease this out for us a little bit more? Dr. Asaf Maoz: Of course, of course. So, the germline defect is in one of the mismatch repair genes, and these genes are responsible for DNA mismatch repair, as their name implies. Now, in a normal cell, we think that one working copy is generally enough to maintain the mismatch repair machinery intact. What happens in tumors, as you alluded to, is that there is a second hit in the same mismatch repair gene that has the pathogenic germline variant, and that causes the mismatch repair machinery not to work anymore. And so what happens is that there is formation of mutations in the cancer cell that are not present in other cells in the body. And we know that there are specific types of mutations that are associated with defects in mismatch repair mechanisms, and those are associated a lot of times with frameshift mutations. And we have termed them ‘microsatellites'. So there are areas in the genome that have repeats, for example, you know, if you have AAAA or GAGA, and those areas are particularly susceptible to mutations when the mismatch repair machinery is not working. And so we can measure that with DNA microsatellite instability testing. But we can also get a sense of whether the mismatch repair machinery is functioning by looking at protein expression on the surface of cancer cells and by doing immunohistochemistry. More recently, we're also able to infer whether the mismatch repair machinery is working by doing next-generation sequencing and looking at many, many microsatellites and whether they have this DNA instability in the microsatellites. Dr. Rafeh Naqash: Excellent explanation. As a segue to what you just mentioned, and this reminds me of some work that one of my good friends, collaborators, Amin Nassar, whom you also know, I believe, had done a year and a half back, was published in Cancer Cell as a brief report, I believe, where the concept was that when you look at these mismatch repair deficient cancers, there is a difference between NGS testing, IHC testing, and maybe to some extent, PCR testing, where you can have discordances. Have you seen that in your clinical experience? What are some of your thoughts there? And if a trainee were to ask, what would be the gold standard to test individuals where you suspect mismatch repair deficient-related Lynch syndrome cancers? How would you test those individuals? Dr. Asaf Maoz: We do sometimes see discordance, you know, from large series, the concordance rate is very high, and in most series it's over 95%. And so from a practical perspective, if we're thinking about the recommendation to screen all colorectal cancer and all endometrial cancer for mismatch repair deficiency, I think either PCR-based testing or immunohistochemistry is acceptable because the concordance rate is very high. There are rare cases where it is not concordant, doing multiple of the tests makes sense at that time. If you think about the difference between the tests, the immunohistochemistry looks at protein expression, which is a surrogate for whether there is mismatch repair deficiency or not, right? Because ultimately, the mismatch repair deficiency is manifested in the mutations. So if the PCR does not show microsatellite instability and now NGS does not show microsatellite instability, the IHC may be a false positive. At the end of the day, the functional analysis of whether there are actually unstable microsatellites either by PCR or by NGS is what I would consider more informative. But IHC again is an excellent test and concordant with those results in over 95% of cases. Now there is also an issue of sampling. It's possible that there's heterogeneity within the tumor. We published a case in JCOPO about heterogeneity of the mismatch repair status, and that was both by immunohistochemistry, but also by PCR. So there are some caveats and interpreting these tests does require some expertise, and I'm always happy to chat with trainees or whoever has an interesting or challenging case. Dr. Rafeh Naqash: Thanks again for that very easy to understand explanation. Now going to management strategies, could you elaborate a little bit upon the neo-adjuvant data currently, or the metastatic data which I think more people are familiar with for immunotherapy in individuals with MSI-high cancers? Dr. Asaf Maoz: Yeah, that's an excellent question and obviously a very broad topic. Individuals with Lynch syndrome typically develop tumors that are mismatch repair deficient or microsatellite unstable. And we have seen over the last 15 years or so that these tumors, because they have a lot of mutations and because these mutations are very immunogenic, we have seen that they respond very well to immunotherapy. And this has been shown across disease sites and has been shown across disease settings. And for that reason, immunotherapy was approved for MSI-high or mismatch repair deficient cancer regardless of the anatomic site. It was the first tissue-agnostic approval by the FDA in 2017. And so there are exciting studies both in the metastatic setting where we see individuals who respond to immunotherapy for many years, and one could wonder whether their cancer is going to come back or not. And also in the earlier setting, for example, the Cercek et al. study in the New England Journal from Sloan Kettering, where they showed that neoadjuvant immunotherapy can cause durable responses for rectal cancer that is mismatch repair deficient. And in that series, the patients did not require surgery or radiation, which is standard of care for rectal cancer otherwise. And there's also exciting data in the adjuvant space, as was presented in ASCO by Dr. Sinicrope, the ATOMIC study, and many more efforts to bring immunotherapy into the treatment landscape for individuals with MSI-high cancer, including individuals with Lynch syndrome. Dr. Rafeh Naqash: A lot of activity, especially in the neo-adjuvant and adjuvant space over the last two years or so. Now going to the actual reason why we are here is your study. Could you tell us why you looked at this idea of patients who had Lynch syndrome and died, and the reasons for their death? What was the thought that triggered this project? Dr. Asaf Maoz: As we were talking about, we now know that immunotherapy really has changed the treatment landscape for individuals with Lynch syndrome, and that most cancers that individuals with Lynch syndrome do have this mismatch repair deficiency. But we also know that individuals with Lynch syndrome can develop tumors that do not have mismatch repair deficiency, and we call them mismatch repair proficient or microsatellite stable. And there was a series from Memorial Sloan Kettering showing that in colorectal cancer, about 10% of the tumors that individuals with Lynch syndrome developed did not have mismatch repair deficiency. In addition to that, we anecdotally saw that some of our patients with Lynch syndrome died of causes that were not mismatch repair deficient tumors. We wanted to see how that has changed since immunotherapy was approved in a tissue-agnostic manner, meaning that we could look at this regardless of where the cancer started, because we would anticipate that if the tumor was mismatch repair deficient, the patient would be able to access immunotherapy as standard of care. Dr. Rafeh Naqash: Thank you. And then you looked at different aspects of correlations with regards to individuals that had an MSI-high cancer with Lynch syndrome or an MSS cancer with Lynch syndrome. Could you elaborate on some of the important findings that you identified as well as some of the unusual findings that perhaps we did not know about, even though the sample size is limited, but what were some of the unique things that you did identify through this project? Dr. Asaf Maoz: The first question was what cause is leading to death in individuals with Lynch syndrome? And we had 54 patients that we identified that had died since the approval of immunotherapy in 2017, 44 of which died of cancer-related causes. And when we looked at cancer-related causes of death, we wanted to know how many of those were due to mismatch repair deficient tumors versus mismatch repair proficient tumors or MS-stable tumors. And we found, somewhat surprisingly, that 43% of patients in our cohort actually died of tumors that were microsatellite stable or mismatch repair proficient, meaning of tumors that are not typically associated with Lynch syndrome. This is not entirely surprising as a cause of death because we know that immunotherapy does not typically work for tumors that are microsatellite stable. And so in the metastatic setting, there are much less cases of durable remissions with treatment. But it was helpful to have that figure as an important benchmark. There are previous studies about causes of death in Lynch syndrome, and particularly from the Prospective Lynch Syndrome Database in Europe. Those have provided really important information about cause of death by cancer site, but they typically don't have mismatch repair status and are more difficult to interpret in that regard. They also don't include a large number of individuals who have PMS2 Lynch syndrome, which is the most common, but least penetrant form of Lynch syndrome. Dr. Rafeh Naqash: As far as the subtype of pathogenic germline variants is concerned, did you notice anything unusual? And I've always had this question, and you may know more about this data, is: In the bigger context of immunotherapy, does the type of the pathogenic germline variant for Lynch syndrome associated MSI-high cancers, does that impact or have an association with the kind of outcomes, how soon a cancer progresses or how many exceptional responders perhaps with MSI-high cancers actually have a certain specific pathogenic germline variant? Dr. Asaf Maoz: That's an excellent question, and certainly we need more data in that space. We know that the type of germline mutation, or the gene in which there is a germline pathogenic variant, determines to a large degree the cancer risk, right? So we know that individuals who have germline pathogenic variants in MLH1 or MSH2 have a much higher colorectal cancer risk than, for example, PMS2. We know that for PMS2, the risks are more limited to colorectal and endometrial, and may be lower risk of other cancers. We also know that, you know, the spectrum of disease may change based on the pathogenic germline variants. For example, individuals who have MSH2 associated Lynch syndrome have more risk of additional cancers in other organs like the urinary tract and other less common Lynch-associated tumors. The question about response to therapy is one where we have much less information. There are studies that are trying to assess this, but I don't think the answer is there yet. Some of the non-clinical data looks at how many mutations there are based on the pathogenic variant and what the nature of those mutations are, whether they're more frameshift or others. But I think we still need more clinical data to understand whether the response to immunotherapy differs. It's also complicated by the fact that the immunotherapy landscape is changing, especially in the metastatic setting, now with the approval of combination ipilimumab and nivolumab for first-line treatment of colorectal cancer that is microsatellite unstable. But in our study, we did find that, as you would expect, there is an enrichment in MS-stable cancers among those with PMS2 Lynch syndrome. Again, our denominator is those who died, right? So this is not the best way to look at the question whether this is overall true, that is more addressed by the study that Sloan Kettering published. But we do see, as we would anticipate, that there are more microsatellite stable cancers among those with PMS2 Lynch syndrome that died. Dr. Rafeh Naqash: A lot to uncover there for sure. This study and perhaps some of the other work that you're doing is slowly advancing our understanding of some of these concepts. So I'd like to shift gears to a couple of provocative questions that I generally like to ask. The first is, in your opinion, and you may or may not have data to back this up, which is okay, and that's why we're having a conversation about it. In your opinion, do you think the type or the quality of the neoantigen is different based on the pathogenic germline variant and a Lynch syndrome associated MSI-high cancer? Dr. Asaf Maoz: I think there are some data out there that, you know, I can't cite off the top of my mind, but there are some data out there that suggest that that may be the case. I think the key question is the quality, right? I think that whether these differences that are found on a molecular level also translate to a clinical difference in response is something that is unknown at this moment. Some people hypothesize that if the tumor has less neoantigens, there's less of a response to immunotherapy. But I think we really need to be careful before making those assertions on a clinical level. I do think it's a really important question that needs to be answered, among others because, you know, in the colorectal space, for example, where we have both the option of doing ipilimumab with nivolumab and the option of doing pembrolizumab, we don't really know which patients need the CTLA-4 blockade versus which patients can receive PD-1 blockade alone and avoid the potential excess toxicity of the CTLA-4 blockade. There are a lot of interesting questions there that still need to be answered. And of course, individuals with Lynch syndrome are just a fraction of those individuals who have MSI-high cancer. So there's also the question about whether non-Lynch syndrome associated MSI-high cancer responds differently to immunotherapy than Lynch syndrome associated MSI-high cancer. A lot of very interesting questions in the field for sure. Dr. Rafeh Naqash: Absolutely. My second question is more about trying to understand the role of ctDNA, MRD monitoring in individuals with Lynch syndrome. If somebody has a germline, you know, Lynch syndrome MSI-high cancer, when you do a tumor-informed ctDNA assessment, what do you capture generally there? Because, and this question stems from a discussion I've had with somebody regarding EGFR lung cancer, since I treat individuals with lung cancer, and the concept generally is that even if the tissue showed EGFR, but for MRD monitoring, when you do a barcoded sequence of different tumor specific mutations, it's not actually the EGFR that they track in the blood when they do ctDNA assessment. But from a Lynch syndrome standpoint, if you have a germline, right, which is the first hit, and then you have the somatic in the tumor, which is the second hit, are you aware or have you tried to look into this where what is exactly being followed if one had to follow MRD in a Lynch syndrome MSI-high colorectal cancer? Dr. Asaf Maoz: I think a lot of the MRD assays are proprietary, and so we don't receive information about what the mutations that are being tracked are. In general, the idea is to track mutations that we would not expect to disappear as part of resistant mechanisms. We want these to be truncal mutations. We want these to be mutations in which resistance is not expected to result in reversion mutations. But what specifically is being tracked is something that I don't know because these assays, the tumor-informed ones, are proprietary, and we don't get the results regarding specific mutations. When it's circulating tumor DNA that is not necessarily tumor-informed, we do get those results, but that is less so about the specific selection of mutations. Dr. Rafeh Naqash: Thank you for clarifying that question to some extent, of course, as you said, we don't know a lot, and we don't know what we don't know. That's the most important thing that I've learned in the process of understanding precision medicine and genomics, and it's a very fast-paced evolving field. Last question related to your project, what is the next step? Are you planning any next steps as a bigger multicenter study or validation of some sort? Dr. Asaf Maoz: There are two big questions that this study raises. One, is this true across multiple other sites, right? Because this is a single center study, and we really need additional centers to look at their data and validate whether they are also seeing that a substantial portion of deaths in individuals with Lynch syndrome are attributable to mismatch repair proficient cancer. The other question is whether we can look at specifically MSI-high cancer versus MS-stable cancer and understand what the mortality rate for each of those are. From a clinical perspective, it's important to counsel individuals with Lynch syndrome about general cancer screening outside of mismatch repair deficient tumors and to understand that there is also a risk of mismatch repair proficient tumors and that treatment for those tumors would be different. There's a lot of work to be done in the future. Another major area of need is to see whether tumors that are microsatellite stable can be sensitized to immunotherapy, and that is beyond the Lynch syndrome field, but that is something that certainly would benefit these individuals with Lynch syndrome who develop mismatch repair proficient cancer. Dr. Rafeh Naqash: That's very interesting to hear, and we'll look forward to seeing some of those developments shape in the next few years. Now, I'd like to spend a minute, minute and a half on you specifically as a researcher, clinician, scientist. Could you briefly highlight - because I remember meeting you several years back as a trainee, with your interest in genomics, computational research - could you briefly tell us what led you to hereditary cancer syndromes based on your research and work? What are some of the things that you learned along the way that other early career investigators can perhaps take lessons from? Dr. Asaf Maoz: Big questions there, thanks for asking. I got interested in the field of hereditary cancer syndromes when I came to the United States and started doing lab research in Stephen Gruber's lab at the time at USC. He's now at City of Hope. And my interest was originally looking at immunotherapy and immunology, but I went to the case conferences where we were learning about individuals with hereditary cancer, and those were kind of earlier days where we were still trying to figure out how to test and what the implications for these individuals would be. And through fellowship, I was also very interested in that, and I did my senior fellowship years with Dr. Yurgelun here at Dana-Farber, who is the director of the Lynch Syndrome Center. And I I think it's the combination between being able to treat individuals based on precision medicine and what the germline mutation is, but also the ability to prevent cancer and to develop strategies to intercept cancer early that is really appealing to me in this field. It's also a great field to be in because it's a small field. If you come to the CGA-IGC meeting, you'll be able to interact with everyone. Everyone is super collaborative, super nice, and I really recommend it to trainees. The CGA-IGC annual meeting is really a great opportunity to learn more and experience some of the advancement specifically in the GI hereditary space. Lessons for trainees. I think there are a lot of lessons that I could think about, but I think finding strong and supportive mentors is one of the things that has helped me most. I think that just having close relationship with your mentor, having frequent discussions and honest discussions about what is feasible, what is going to make a difference for your patients and your research and what you want to focus on is really important. And so I think if I had to choose one thing, I would say choose a mentor that you trust, that you feel you have a good relationship with, and that has the availability to support you. Dr. Rafeh Naqash: Thank you so much for those insightful comments, and thank you for sharing with us your journey, your project, and some of your interesting thoughts on this concept of hereditary cancers. Hopefully, we'll see more of this work being published in JCOPO through your lab or work from others. Dr. Asaf Maoz: Thank you so much. I appreciate the opportunity to be here. Dr. Rafeh Naqash: 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.

Cancer used to be something you worried about later in life — but not anymore. More and more young adults are being diagnosed, and doctors are trying to figure out why this is happening. Dr. Sanjay Gupta talks with oncologist Dr. Kimmie Ng about what's behind this rise, why colorectal cancer is leading the trend, and the signs you shouldn't ignore.  You can find more information and resources at the Young-Onset Colorectal Cancer Center at the Dana-Farber Cancer Institute.    This episode was produced by Kyra Dahring.    Medical Writer: Andrea Kane Showrunner: Amanda Sealy Senior Producer: Dan Bloom Technical Director: Dan Dzula  Learn more about your ad choices. Visit podcastchoices.com/adchoices

Dr Jeremy S Abramson from Massachusetts General Hospital in Boston, Dr Jennifer Crombie from Dana-Farber Cancer Institute also in Boston and Dr Laurie H Sehn from the BC Cancer Centre for Lymphoid Cancer in Vancouver, British Columbia, Canada, discuss recent updates on available and novel treatment strategies for follicular lymphoma.  CE information and select publications here.

On this episode of SurgOnc today, Dr. Rosalinda Alvarado and Dr. George Molina moderate a discussion on how to improve the recruitment of Hispanic/Latino patients into clinical trials. Joining the conversation are Jeanette Gonzalez from the University of Illinois Cancer Center and Alas-Wings, Dr. Narjust Florez from Dana-Farber Cancer Institute and Harvard Medical School, and Dr. Kennedy Timothy from MedStar Health and Georgetown University.

Scott A. Armstrong, M.D., Ph.D., of the Dana-Farber Cancer Institute, studies how certain aggressive forms of acute myeloid leukemia (AML) develop and survive. His work centers on a protein called menin, which helps leukemia cells keep cancer-promoting genes switched on. Armstrong's team has found that blocking menin with specially designed drugs can shut down these gene programs, push leukemia cells to mature, and slow or stop the disease in lab models and patients. While some leukemias adapt by developing mutations in menin or finding other ways to survive, his research is revealing why certain genes are especially dependent on menin and how to target them more effectively. These discoveries are now shaping new treatments, drug combinations, and potential strategies for other cancers that rely on similar mechanisms. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40875]

Scott A. Armstrong, M.D., Ph.D., of the Dana-Farber Cancer Institute, studies how certain aggressive forms of acute myeloid leukemia (AML) develop and survive. His work centers on a protein called menin, which helps leukemia cells keep cancer-promoting genes switched on. Armstrong's team has found that blocking menin with specially designed drugs can shut down these gene programs, push leukemia cells to mature, and slow or stop the disease in lab models and patients. While some leukemias adapt by developing mutations in menin or finding other ways to survive, his research is revealing why certain genes are especially dependent on menin and how to target them more effectively. These discoveries are now shaping new treatments, drug combinations, and potential strategies for other cancers that rely on similar mechanisms. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40875]

Scott A. Armstrong, M.D., Ph.D., of the Dana-Farber Cancer Institute, studies how certain aggressive forms of acute myeloid leukemia (AML) develop and survive. His work centers on a protein called menin, which helps leukemia cells keep cancer-promoting genes switched on. Armstrong's team has found that blocking menin with specially designed drugs can shut down these gene programs, push leukemia cells to mature, and slow or stop the disease in lab models and patients. While some leukemias adapt by developing mutations in menin or finding other ways to survive, his research is revealing why certain genes are especially dependent on menin and how to target them more effectively. These discoveries are now shaping new treatments, drug combinations, and potential strategies for other cancers that rely on similar mechanisms. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40875]

Scott A. Armstrong, M.D., Ph.D., of the Dana-Farber Cancer Institute, studies how certain aggressive forms of acute myeloid leukemia (AML) develop and survive. His work centers on a protein called menin, which helps leukemia cells keep cancer-promoting genes switched on. Armstrong's team has found that blocking menin with specially designed drugs can shut down these gene programs, push leukemia cells to mature, and slow or stop the disease in lab models and patients. While some leukemias adapt by developing mutations in menin or finding other ways to survive, his research is revealing why certain genes are especially dependent on menin and how to target them more effectively. These discoveries are now shaping new treatments, drug combinations, and potential strategies for other cancers that rely on similar mechanisms. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40875]

Scott A. Armstrong, M.D., Ph.D., of the Dana-Farber Cancer Institute, studies how certain aggressive forms of acute myeloid leukemia (AML) develop and survive. His work centers on a protein called menin, which helps leukemia cells keep cancer-promoting genes switched on. Armstrong's team has found that blocking menin with specially designed drugs can shut down these gene programs, push leukemia cells to mature, and slow or stop the disease in lab models and patients. While some leukemias adapt by developing mutations in menin or finding other ways to survive, his research is revealing why certain genes are especially dependent on menin and how to target them more effectively. These discoveries are now shaping new treatments, drug combinations, and potential strategies for other cancers that rely on similar mechanisms. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40875]

Here in the West, acupuncture often feels like something foreign, something patients approach with curiosity but no context. “I don't know anything about Chinese medicine,” they'll say. And most of the time, that's true. We didn't grow up with an uncle who prescribed herbs or a parent using needles to ease the illnesses and injuries of childhood.For Wei Dong Lu, medicine wasn't foreign at all. He grew up inside it, part of a family where healing was daily life. At sixteen, during the Cultural Revolution, he was told to learn a “practical skill.” His classmates were sent to carpentry or sewing. He was handed needles. Listen into this discussion as we trace the path that took him from Shanghai to Nebraska, from teaching at the New England School of Acupuncture to practicing oncology acupuncture at Harvard's Dana-Farber Cancer Institute.What you'll hear isn't just the biography of one practitioner, but a story about how medicine travels—how it bends and blends to circumstance, how it adapts to new settings, and how something essential continues to move through it all.

If more and more young people are dying of colorectal cancer, why aren't we talking about it? Is it because we're too ashamed of our bodies?Rates of colorectal cancer are rising, especially for people under 50. But it's hard to raise awareness for a cancer that a lot of us find hard to talk about. In a recent essay for The Cut, writer Laurie Abraham described her experience of colon cancer, which included a lot of embarrassment. Talking about your bowel movements is...not fun. Can you relate?Today, Brittany is joined by Laurie and Dr. Kimmie Ng, Co-Director of the Colon and Rectal Cancer Center at the Dana-Farber Cancer Institute, to get into the cultural shame around how we talk about colon cancer - and how that extends to a lack of funding and research.Follow Brittany Luse on Instagram: @bmluseFor handpicked podcast recommendations every week, subscribe to NPR's Pod Club newsletter at npr.org/podclub.Learn more about sponsor message choices: podcastchoices.com/adchoicesNPR Privacy Policy

In this episode, Sara Tolaney, MD, of Dana-Farber Cancer Institute, discusses sequencing strategies after progression in...

In this episode, Sara Tolaney, MD, of Dana-Farber Cancer Institute, discusses sequencing strategies after progression in HER2-positive metastatic breast cancer. She reviews current second-line standards, considerations for patients with brain metastases, and emerging therapies in the post–T-DXd setting.Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

Dr. Lachelle Weeks is a physician-scientist at Dana-Farber Cancer Institute working on a project to predict leukemia risk based on widely available blood samples.

Shoot us a Text.On this Saturday, Chris joins Paul and Kyle to talk about the power of remembrance and how Carla Cosenzi and TommyCar Auto Group are connecting people in a meaninful way through the 17th Annual Tom Cosenzi Driving for the Cure Charity Golf Tournament.Founded in memory of Tom Cosenzi, the event supports Dana-Farber Cancer Institute and the incredible work of Dr. Wen and his team.Golfers, sponsors, and volunteers showed up in full force to continue the mission of giving back.Carla Cosenzi on LinkedIn said “Dad, I hope you are proud of what has been built in your name… Together, we are making a difference.”Join Paul J Daly and Kyle Mountsier every morning for the Automotive State of the Union podcast as they connect the dots across car dealerships, retail trends, emerging tech like AI, and cultural shifts—bringing clarity, speed, and people-first insight to automotive leaders navigating a rapidly changing industry.Get the Daily Push Back email at https://www.asotu.com/ JOIN the conversation on LinkedIn at: https://www.linkedin.com/company/asotu/

Small cell lung cancer was once considered one of the most challenging diagnoses in oncology. But today, groundbreaking treatments are transforming patient outcomes and rewriting survival stories. Discover how immunotherapy, T-cell engagers, CAR T-cell therapy, and antibody drug conjugates are moving from clinical trials to standard care, offering patients years of disease control and genuine hope for the future. Featuring insights from Dr. Jacob Sands, thoracic oncologist at Dana-Farber Cancer Institute, and inspiring patient advocate Wendy Brooks, who shares her powerful journey from early detection through cutting-edge clinical trials, proving that advocacy and hope can change everything. Guests: Dr. Jacob Sands, Oncologist, Dana-Farber Cancer Institute Courtney Mantz, Program Manager II, SCLC Program, Dr. Sands' Assistant. Dana-Farber Cancer Institute, Lowe Center for Thoracic Oncology Wendy Brooks, Patient Advocate Show Notes | Transcript | Watch Video

Hart and Fitzy recap a record-setting WEEI/Nesn Jimmy Fund Radio-Telethon where we raised $5.7 million for The Jimmy Fund and Dana-Farber. The Red Sox dropped a two game series to the Orioles in rough fashion after failing to convert with runners in scoring position multiple times.

Hart and Fitzy recap a record-setting WEEI/NESN Jimmy Fund Radio-Telethon. Why didn't the Red Sox send Nate Eaton home last night in extra innings? Could their upcoming series with the Yankees determine the season?

Christopher Lathan, MD, Chief Clinical Access Officer, Dana-Farber Cancer Institute ● Dr. Christopher Lathan is the Chief Clinical Access Officer at Dana-Farber, founding Director of the Cancer Care Access Program and a clinical oncologist focusing on lung cancer. ● His research is centered on the effects of race, class, and access to care in cancer outcomes, including racial disparities in lung cancer treatment, differences in access to precision medicine by race and social class and equitable distribution of new treatment across historically marginalized populations. ● Dr. Lathan aims to bridge the gap between research in disparities and the realities of patient care by developing interventions to increase access to high quality care, developed in part through community engagement.

Emily Bailey, nurse navigator, Jimmy Fund Clinic, Dana-Farber Cancer Institute, and Amelia “Mia” McDonough, nurse, Jimmy Fund Clinic, Dana-Farber Cancer Institute ● Emily graduated from University of North Carolina Wilmington in 2018. She has been a nurse for eight years transitioning from the population of adult solid tumor oncology to pediatric oncology. ● At the Jimmy Fund Clinic, she is solid tumor nurse navigator. As a nurse navigator, she assists with guiding young patients and their families through the complex cancer diagnosis and treatment. They coordinate care and provide continuous education and support. ● In her free time, Emily enjoys running and will be running the Boston Half presented by Dana-Farber and Jimmy Fund in November. About Mia McDonough ● Amelia grew up in Dedham and graduated from Villanova University in Pennsylvania. She's had multiple family members treated at Dana-Farber as adult patients and always knew Dana-Farber was a special place. ● Amelia joined the Jimmy Fund Clinic as a nurse in 2024. In the infusion room, she has anywhere from four to six patients per day - they maybe getting chemotherapy, blood products, or coming in for sick visits. She is responsible for coordinating with their providers to make sure they get all they need while they're in the infusion chair.

Christopher Lathan, MD, Chief Clinical Access Officer, Dana-Farber Cancer Institute ● Dr. Christopher Lathan is the Chief Clinical Access Officer at Dana-Farber, founding Director of the Cancer Care Access Program and a clinical oncologist focusing on lung cancer. ● His research is centered on the effects of race, class, and access to care in cancer outcomes, including racial disparities in lung cancer treatment, differences in access to precision medicine by race and social class and equitable distribution of new treatment across historically marginalized populations. ● Dr. Lathan aims to bridge the gap between research in disparities and the realities of patient care by developing interventions to increase access to high quality care, developed in part through community engagement.

Anne Gross, PhD, RN, FAAN, Senior Vice President of Patient Care Services, Chief Nursing Officer, Ning Zhao Chair of Nursing, Dana-Farber Cancer Institute ● Anne is responsible for adult and pediatric nursing across all care sites at Dana-Farber, The Phyllis F. Cantor Center for Research in Nursing and Patient Care Services, and the Center for Clinical and Professional Development. She also oversees a variety of other clinical services, patient and family programs, and Volunteer Services. ● Since joining Dana-Farber in 2002, she has led implementations of a primary nursing care model and a residency training program for newly licensed nurses and has secured funding for programs and research to support inclusion, diversity and equity, positive practice environments, and self-care and renewal programs. She also is involved in committees, boards, and initiatives nationally and internationally and is a Fellow in the American Academy of Nursing.

“At least some of the answer to these issues of compassion fatigue and burnout have to do making our practice environments the very, very best they can be so that nurses and other clinicians can really connect and care for patients in the ways that they want to be able to do that—and the patients need them to be able to do. I think there's a lot that is here already and will be coming, and I feel pretty optimistic about it,” ONS member Anne Gross, PhD, RN, NEA-BC, FAAN, senior vice president for patient care services and chief nursing officer at Dana-Farber Cancer Institute in Boston, MA, told ONS member Christine Ladd, MSN, RN, OCN®, NE-BC, member of the ONS 50th anniversary committee, during a conversation about burnout and compassion fatigue in oncology nursing. Ladd spoke with Gross and ONS member Tracy Gosselin, PhD, RN, NEA-BC, AOCN®, FAAN, senior vice president and chief nursing executive at Memorial Sloan Kettering Cancer Center in New York, NY, about the history of nurse well-being and how nurses and health systems are approaching it today. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Episode Notes  This episode is not eligible for NCPD.  ONS Podcast™ episodes: ONS 50th anniversary series Episode 315: Processing Grief as an Oncology Nurse Episode 292: What We Need to Do to Retain Today's Oncology Nursing Workforce Episode 291: Build a Sense of Belonging for Nurses and Patients Episode 264: Stop the Stressors and Improve Your Mental Health as a Nurse Episode 246: Create a Culture of Safety: Fair and Just Culture Episode 160: Build Innovative Staff Education Tools and Resources ONS Voice articles: Critical Event Debriefings Can Reduce Oncology Nurses' Risk of Compassion Fatigue and Burnout ONS Chapters and DNP Candidates Combine Forces to Support Oncology Nurse Well-Being Step Out of Reality With Virtual Breaks to Support Your Wellness at Work Clinical Journal of Oncology Nursing articles: Burnout and Well-Being: Evaluating Perceptions in Bone Marrow Transplantation Nurses Using a Mindfulness Application Engaging Nurse Residents Through Poetry Strategies to Mitigate Moral Distress in Oncology Nursing ONS Nurse Well-Being Learning Library ONS Communities ONS Chapters Connie Henke Yarbro Oncology Nursing History Center Oncology Nursing Foundation Resiliency Resources 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 Gross: “I was on an oncology unit early in practice. And just like today, we were dealing with very sick patients. We were dealing with death and dying. We were administering very toxic treatments and really pushing a field forward in oncology. So there were similar challenges, but I think different from today. There weren't the kind of resources; there wasn't the body of work that's been done today around compassion fatigue and burnout, work-life balance, and things like that. There was not that body of literature and science like there is today. And so there was more of a grassroots kind of support building in the clinical environment that I think I experienced.” TS 2:35 Gosselin: “I think there's also a piece when we think about nurses in the work we do—we also have families. We have aging parents and children. And sometimes that burnout is multifactorial in that we have family obligations and other obligations that make it really hard. And for some people, they say work is their escape from some of that. Yet it's all hard to balance sometimes.” TS 8:09 Gosselin: “It's this question that people like Anne, myself, other chief nurses are saying. If we add this new technology, what are we going to take away? Do we need another alarm to ring to the phone or to their badge? How much can you ask people to do and not be distracted when they're at point of care delivering patient care? Technology should never be a distractor, nor should it tell us how to practice. The technologies we have today—I'm like, ‘Wow, I wish I had that when I started my career.' And yet there's also a double-edged sword to that. I think we have to balance when we think about care and care delivery.” TS 16:36 Gross: “There are so many resources, first of all, that ONS provides to all of us at all levels and in all points in our career and our path from novice to experts. And the needs, though, are the same. Whether you're a novice nurse or whether you're a very experienced nurse, you need to continue to learn and to get new information, and ONS is an incredible resource for that. … As I think both of us keep alluding to and emphasizing here, you also need that connection to other people. And that's what ONS provides—that opportunity to get connected to other people that might be working in some other part of the country or other part of the world but is dealing with similar things that you're dealing with. So it provides that opportunity, and then it also provides an opportunity to get involved. I think when you can get involved and be part of solving a problem, it doesn't then control you and you won't feel defeated by it.” TS 22:24