Treatment of Multiple Myeloma: ASCO-OH (CCO) Living Guideline

Dr. Lisa Hicks and Dr. Joseph Mikhael discuss the updated guideline from ASCO and Ontario Health (Cancer Care Ontario) on the treatment of multiple myeloma. They cover recommendations for therapeutic options across smoldering multiple myeloma, transplant eligible multiple myeloma, transplant ineligible multiple myeloma, and relapsed or refractory multiple myeloma. They highlight the importance of shared decision making and patient-centric care. They comment on the explosion of new treatment options in this space and the impetus for this guideline becoming a living guideline, which will be updated on an ongoing, regular basis. Read the full guideline, "Treatment of Multiple Myeloma: ASCO-Ontario Health (Cancer Care Ontario) Living Guideline" at www.asco.org/hematologic-malignancies-guidelines. TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/hematologic-malignancies-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-25-02587   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. Lisa Hicks from St. Michael's Hospital and University of Toronto, and Dr. Joseph Mikhael from the Translational Genomics Research Institute, an affiliate of City of Hope Cancer Center, co-chairs on "Treatment of Multiple Myeloma: American Society of Clinical Oncology-Ontario Health (Cancer Care Ontario) Living Guideline." Thank you for being here today, Dr. Hicks and Dr. Mikhael. Dr. Lisa Hicks: Thanks so much. Dr. Joseph Mikhael: It is a pleasure to be with you, Brittany. Thank you. Brittany Harvey: 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. Hicks and Dr. Mikhael 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 what we are here today to talk about, Dr. Mikhael, I would like to start by recognizing that this guideline updates the 2019 ASCO-CCO Guideline on the Treatment of Multiple Myeloma. So what prompted this update and what is the scope of this updated guideline? Dr. Joseph Mikhael: It is amazing when we think back in myeloma years, 2019 actually seems a very, very long time ago because really so much has changed in myeloma over these last six to seven years. Indeed, there have been over 150 randomized controlled trials that we didn't have at the prior guideline that we reviewed for this. Myeloma is a disease that has really changed so dramatically over these last several years. Multiple new agents have been introduced. We now have CAR-T cell therapy, bispecific antibodies, and multiple other agents that were not available at the time. Furthermore, with this growing complexity, it is becoming more important than ever to be able to provide practical advice and guidelines to the oncology community. For most oncologists, they have less than 5% of their time dedicated to multiple myeloma. It is important to bring a clarity to them that allows them to care for their patients. And the scope of these guidelines, furthermore, really cover the whole spectrum of myeloma. They go further than our prior guideline where now we have included smoldering multiple myeloma along with frontline therapy and relapsed multiple myeloma. So, we have really tried to provide the full spectrum to our colleagues in oncology to ensure that they have the tools they need to provide the best care possible for their patients. Dr. Lisa Hicks: That is a really terrific summary. And maybe one thing I will just add is it is really unique to have this much literature. I can't think of another guideline that I have ever been involved with that has seen a field move so quickly and develop so many advancements in a period of just over four or five years. Brittany Harvey: Certainly, there is a large volume of evidence that you all had to review for this guideline update. I think to your point probably one of the greater volumes of literature for a guideline update that you both mentioned. Based on that, I would like to review the key recommendations that are updated in this guideline. So Dr. Hicks, that new patient population that Dr. Mikhael mentioned earlier, what are the key recommendations for patients with smoldering multiple myeloma? Dr. Lisa Hicks: So this is the first time that an ASCO guideline is addressing this branch of multiple myeloma care. It is an area where I think some guidance is needed, and smoldering myeloma is not an active cancer. And so one thing that I really want to highlight is that the panel felt very strongly that to recommend any therapy in this space we needed a higher level of evidentiary certainty, of evidentiary confidence, to make recommendations for active therapy. The panel really made two very important recommendations. First of all, the panel did not recommend treatment for low or intermediate risk smoldering myeloma. That is important. And then the area where I think for the first time we have recommended consideration of treatment is patients with high risk smoldering myeloma. And for patients with high risk smoldering myeloma, the panel recommended that it was appropriate to consider either treatment with daratumumab or careful observation. Dr. Joseph Mikhael: And I think that move forward as you have mentioned, Dr. Hicks, is particularly important because it is an area to some degree still of equipoise and many trials are going on in the area. But we do now have a strong phase III trial that supports the use of daratumumab monotherapy for three years when compared to close observation. But of course, that is not for everyone. And one of the key themes of all of our recommendations are going to be now that more and more choices are available, that we have discussions with our patients to ensure that we match the right treatment with the preference of the patient. And I think that is particularly important here in smoldering myeloma. Dr. Lisa Hicks: Multiple myeloma care and the multiple myeloma evidence is really so nuanced, and one of the nuances that readers will appreciate if they read the guideline is that how smoldering myeloma is risk stratified has been different across different trials. And that really adds to the complexity of this recommendation and is one of the reasons that the panel felt that it was appropriate to recommend either observation or treatment. Brittany Harvey: It is great to have these new recommendations for this unique patient population. And as you both mentioned, that individualized patient care is really important across this entire guideline. So then following those recommendations, Dr. Mikhael, what is recommended for initial therapy, autologous stem cell transplantation, post transplant therapy, and measurement of response for patients with transplant eligible multiple myeloma? Dr. Joseph Mikhael: Well, that is an area that has really considerably also grown since the last guideline. Obviously one would have to consult the guidelines to get every last detail, but in essence, we want to assess whether or not patients are transplant eligible or ineligible. And that assessment is not based on age or renal function alone, but indeed on a careful assessment of that patient. When that assessment is made and deemed that a patient is transplant eligible, our recommendation is that a patient typically would receive a quadruplet. That is to say, a monoclonal antibody directed against CD38, a proteasome inhibitor, an immunomodulatory drug, and dexamethasone to be given for approximately four to six cycles followed by the stem cell transplant, followed by potentially another two cycles of consolidation, and then maintenance therapy. A couple of important caveats. One, we do have two different CD38 antibodies that can be used, either daratumumab or isatuximab. Although typically bortezomib is the preferred proteasome inhibitor, consideration can be given to carfilzomib by virtue of the potential toxicity from bortezomib. And then lastly in the maintenance setting, we are typically recommending at least lenalidomide alone, but consideration can be given to dual maintenance therapy as the data is emerging to either add to that daratumumab or carfilzomib. All the while using the IMWG criteria for response. The goal of course is to achieve the deepest response possible and to maintain that response until such time as patients would relapse. Finally, the length of maintenance therapy continues to be an area of equipoise and study in multiple myeloma. And so at minimum, patients would receive two to three years of maintenance therapy, and based on risk status and depth of response it can be considered that patients would potentially come off maintenance therapy, of course always with the caveat that toxicity would influence length of therapy as well. Brittany Harvey: Yes, as you mentioned, evaluating which patients are eligible is extremely important for considering what is recommended in the guideline for both transplant eligible and transplant ineligible patients. So then Dr. Hicks, following those recommendations for transplant eligible multiple myeloma, what are the recommended treatments, goals of therapy, and measurement of response for patients with transplant ineligible multiple myeloma? Dr. Lisa Hicks: You know, I really can't emphasize enough how important an individualized patient assessment is. When we are thinking about the range of patients that are included in this category of transplant ineligible patients, it is a huge range. You may have fairly fit patients in their late 70s all the way to patients in their 90s. And we really want to see that treatments are tailored both to the fitness of the patient, their individual circumstances, and their preferences. And it is a wonderful thing to have lots of options for patients in this circumstance. What the guidelines have recommended for most patients who are transplant ineligible but fit enough for a stronger therapy is quadruplet therapy. So actually therapy that is very similar to what is being recommended in the transplant eligible population but for a longer period of time. And then for those patients who for whatever reason, be it their fitness or their preference, are not appropriate for that quadruplet therapy, the recommendation is for triplet therapy with a combination of lenalidomide, bortezomib, dexamethasone, or very often, more often in most cases, an antibody based approach with an anti-CD38 plus lenalidomide plus dexamethasone. Dr. Joseph Mikhael: The only thing I would add to that, I think we have to also, as we do mention in our recommendations, be particularly cautious with the dosing of these medications. Because even though we think of them as a single agent or a particular class, there can be quite a variation within the dosing regimen that can affect a patient's side effects and their quality of life. And so being very careful with dose modifications, and particularly in the transplant ineligible patient, is an important part of the recommendation as well. Dr. Lisa Hicks: Yeah, this is a podcast so no one can see me nodding vigorously that dose modification is so important particularly with those older and frailer patients, and with particular attention to trying to reduce dexamethasone doses and favoring weekly administration of bortezomib when that drug is used. Brittany Harvey: Absolutely. Considering the risks and benefits and patient preferences is really key to selecting therapy for these patients. So then Dr. Mikhael, for the final overarching patient population addressed in this guideline, for patients with relapsed or refractory multiple myeloma, what treatment options are recommended? Dr. Joseph Mikhael: This of course is, if you will, the biggest part of the guideline because there has been so much done in the relapse setting. And I think we start the guideline by saying a decision has to be made as to when to institute therapy. That there may be some patients with slow biochemical relapse that may be monitored for a period of time. But when the decision is made to initiate treatment, instead of a simple algorithm, the guideline emphasizes the fact that there are multiple choices that can be given to a patient that are going to match what comorbidities the patient has, what they have been treated with before, and of course what their preferences are. I think we highlight two particular areas. That now that CAR-T cell therapy is available as early as first relapse, it should be a consideration by virtue of the fact that it has resulted in such deep and durable responses. But that triplets should also be considered in that earlier relapse setting because we do have multiple classes of agents that can be used. We know that in later relapse options exist including bispecific antibodies for which we have four different choices. And that in general, patients will ultimately receive either a triplet or CAR-T cell therapy in earlier relapse, but there are some patients who may be eligible only for a doublet by virtue of their comorbidities and of their prior therapies. Lastly, it really does emphasize the point as we have mentioned a few times in this podcast, and I am so glad it keeps coming up, is that as I often say we don't treat myeloma, we treat people. And engaging the patient in that conversation to ensure that the right treatment gets matched to the right patients is particularly important because with all the new classes that we have with antibody drug conjugates, with XPO1 inhibitors, the traditional three classes of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, along with as we have already mentioned CAR-T and bispecific antibodies, it really is an incredible laundry list of choice. And making that choice specific to the patient becomes absolutely critical. I should also lastly note that there are patients who may defer their initial transplant. There may be patients who may be eligible for a second transplant. So autologous stem cell transplant, although primarily used in the frontline setting, may still be a consideration for a smaller subset of patients in the relapse setting. Dr. Lisa Hicks: I think maybe one thing that I would add is an overarching principle which is actually similar to a principle in the first guideline, and that is that in the relapsed or refractory setting, there are many different treatment options. And in fact, the number of treatment options feels like it is evolving every day. But an overarching principle for clinicians to consider is to try and choose combinations of drugs that the patient has either not been exposed to in the past or certainly that they are not refractory to. We really want to be pulling new options out of the toolbox as much as we can. Dr. Joseph Mikhael: Very often we do see where someone may be on a triplet and they are progressing on it and someone just changes out one drug. We have suggested not to take that approach but to take the approach of completely introducing a new therapy when someone is progressing on their current therapy. I think that point is particularly important and the consensus panel was very clear. Brittany Harvey: Understood. That is very helpful when thinking about what options to offer to patients in the relapsed and refractory setting. And as you mentioned earlier, the figures in this guideline provide an outline of options and then the tables really go into some of the details and outcomes of the trials, and those are very helpful for clinicians to refer to. So then Dr. Hicks, we have talked a little bit about some of the nuances of the guideline, but what should clinicians know as they implement these new and updated recommendations? Dr. Lisa Hicks: I think they should feel comfortable that these are trustworthy guidelines. So these are evidence-based guidelines that have been rigorously developed after a very thorough evidence review and put together by a panel of experts who were extremely thoughtful in their review of the evidence. And so all of this contributes to the trustworthiness of the guidance. And then I would also encourage people to take a deep look at the guidelines because of the importance of nuance that is addressed in them, and then to also explore some of the tools that ASCO is developing that helps with implementation including the flow charts that are contained within the guidelines and some additional tools that are available online. Brittany Harvey: Absolutely. The tools and resources for this guideline are available online with the publication and we will provide links to that in the show notes of the episode. So then following that, Dr. Mikhael, how does this guideline update affect patients with multiple myeloma? Dr. Joseph Mikhael: As we sort of intimated earlier, I like to say I don't treat myeloma, I treat people. I think we should always be patient-centric and patient-focused. And I think in the discussion we always were. We always wanted to ensure that multiple factors go into a decision-making process. We are not just looking at the biology of the disease, we are looking at patient factors. Those patient factors include their frailty as we commented in a frailty assessment, their preferences, their comorbidities. And I think, in a day where we have so many choices, we emphasize in the guideline the importance of that conversation with the patient. That, if you will, shared decision-making model where options are laid out and based on the patient factors and the treatment factors they can then be meshed together in the best way so that patients can make the right choice. And of course in conjunction with the guidelines, we have patient friendly summaries of them. And we involved, of course, patients in the development of these guidelines. And I think that is one of the greatest strengths of the ASCO guidelines is that there is a patient with us at the table who is giving their perspective on the guideline as we go forward. So I am very thankful that we have created a product that is, if you will, not only for the providers, the practitioners that are prescribing these agents and that are directly giving the care, but indeed for the very patients who of course have the most at stake here. Dr. Lisa Hicks: Yeah Joe, I am so glad you called out the participation of patient partners in the guideline. It is such an important part and they were really- the patient partner was such an important part of this panel in helping us understand the patient perspective as we developed this guidance. Brittany Harvey: Definitely. It is a hugely important role for the panel and for all of the panel including the patient partners and the experts in the disease to review the evidence and come up with comprehensive recommendations. And yes, as you mentioned, the individualized treatment and the shared decision-making is really paramount to this guideline. Finally, Dr. Hicks, you alluded to earlier the vast number of treatment options that is really exploding in multiple myeloma. And so this guideline is becoming a living guideline continuously updated by ASCO. So what are the outstanding questions regarding this topic and what evidence is the panel looking forward to for future updates? Dr. Lisa Hicks: I am really excited about this. This is one of the first guidelines that will be a living guideline for ASCO and it is such a good fit. You have heard Joe and I say a few times how quickly this field is moving, how complex the field is. I think everyone on the panel knew that no matter how quickly we did it and how deeply we reviewed the evidence, it was inevitable that more evidence would be generated as we were putting out the guideline. In a field like that, it is really important that we find a way to provide evidence-based guidelines quickly to the community. You know, waiting another five years, letting another 150 trials accrue before we do another guideline is not what the community needs. And so ASCO has really risen to this challenge and is committed to living guidelines. And so a living guideline is a guideline that commits to reviewing the evolving evidence on an ongoing basis, watching for practice changing trials, and having a standing panel that will review evidence and update recommendations on a regularly scheduled basis. So that is what a living guideline is, and that is what this guideline is becoming. That is just the first thing in terms of what a living guideline is. And then what are we watching? Well, honestly what aren't we watching? There is so much happening in multiple myeloma. We knew as we put the guideline out that there were trials in process, some trials that had been released at conferences but not yet published. We will be waiting for those and if they are practice changing they will be addressed in upcoming updates. There is new evidence just recently presented around combined anti-CD38 and bispecific antibodies. I don't know yet whether that will be addressed but I wouldn't be surprised if it was. There are so many things coming down the pipeline and it is just wonderful that there is going to be a way to try and address them in a robust fashion. Dr. Joseph Mikhael: Yeah I agree with you, Lisa. I can't think of another disease that would be more relevant for a living guideline. I mean we had difficulty because new data kept coming in as we were making recommendations. And so at some point we had to draw a line and say this is where we will stop and produce this guideline and have it ongoing. And I really look forward to seeing the updates because we know as you mentioned that there are so many things that are on the verge of approval and on the verge of changing the way we manage this terrible disease. And before I close, I would love to remind all of our listeners that as we commented from the start, patient engagement is critical at ASCO and in our guidelines process. Unfortunately we lost a very dear patient during the guidelines process, and that is Jack Aiello. Jack Aiello had been a patient and a patient advocate for many, many years in the myeloma community. And indeed we have actually dedicated these guidelines to his honor. And so I thought it would be valuable for us to mention that today. And we miss you Jack, but we are very grateful that we have been able to dedicate this excellent body of work to your memory. Brittany Harvey: Absolutely. This guideline and your dedication to him is an honor to his memory and we really recognize him in thinking about this guideline. We will look forward to those future trial results that you mentioned, Dr. Hicks, to update this guideline and continue to provide options for patients with multiple myeloma and improve upon those options and shared decision-making with patients. So I want to thank you both for all of your work to develop this guideline and for your time today, Dr. Hicks and Dr. Mikhael. Dr. Lisa Hicks: You are so welcome. Thanks for featuring this guideline. Dr. Joseph Mikhael: Thank you so much, Brittany. It has been a privilege. Brittany Harvey: Finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/hematologic-malignancies-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.  

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. 

Dr. Tanya Thomas and Dr. Aparna Jotwani join the podcast to discuss the new Oncology Nursing Society and American Society of Clinical Oncology evidence-based guideline on the management of antineoplastic extravasation. They discuss recommendations from the expert panel on: management of extravasation of vesicant or irritant with vesicant properties antineoplastic agents, management of extravasation of paclitaxel or docetaxel, use & duration of thermal compress, and escalation of care. They share the importance of this comprehensive interdisciplinary guideline, highlight the algorithm as a useful tool for clinicians, and outline the outstanding questions related to the management of extravasation. Read the full guideline, "ONS/ASCO Guideline on the Management of Antineoplastic Extravasation" at www.asco.org/supportive-care-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/supportive-care-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the JCO Oncology Practice, https://ascopubs.org/doi/10.1200/OP-25-00579  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Tanya Thomas, clinical chair of the guideline and clinical nurse specialist from University of Virginia Health, and Dr. Aparna Jotwani, medical oncologist from Baylor College of Medicine, authors on "Management of Antineoplastic Extravasation: Oncology Nursing Society – American Society of Clinical Oncology Guideline." Thank you for being here today, Dr. Thomas and Dr. Jotwani. Dr. Aparna Jotwani: Thank you. Dr. Tanya Thomas: Thank you for having us. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Thomas and Dr. Jotwani, who have joined us here today, are available online with the publication of the guideline in JCO Oncology Practice, which is linked in the show notes. So then to dive into the content here, Dr. Thomas, could you start us off by providing an overview of both the scope and the objectives of this guideline? Dr. Tanya Thomas: Yes, so the objective of this guideline is to provide the evidence-based recommendations to help support our interdisciplinary teams, including the oncologist, the advanced practice providers, pharmacists, and nurses who are involved in the care and management of patients who are experiencing an extravasation of an antineoplastic agent. While rare, the antineoplastic and certain chemotherapy extravasations are oncologic emergencies. The recommendations are to minimize negative consequences and provide a standardized approach to the care when such an event occurs. Dr. Aparna Jotwani: I would add that our scope is limited to intravenous antineoplastic vesicants, irritants, and irritants with vesicant potential. The scope of the guideline applies to the care team for adult oncology patients receiving treatments through venous access. Outside the scope is management of extravasation during other routes of treatment administration, such as intraperitoneal, intravesical, and hepatic arterial infusion. Our recommendations regarding vascular access for therapy or interventions to prevent extravasations are also outside of the scope for this guideline. Brittany Harvey: Understood. I appreciate that background and understanding what's in scope and what's out of scope for this guideline. So then I'd like to pivot and talk about the key recommendations of this guideline across the clinical questions. So first, Dr. Jotwani, what does the panel recommend for patients with extravasation of vesicant or irritant with vesicant properties antineoplastic agents? Dr. Aparna Jotwani: The panel strongly recommends for all classes where an antidote exists to proceed with using the antidote. Recommendations for paclitaxel and docetaxel are specifically addressed in a recommendation. This is further detailed in Tables 1 and 4 within the guideline. Evidence on the use of antidotes for extravasation is limited to nonrandomized, uncontrolled, observational studies and case series. Placebo-controlled trials on this topic would be unethical. There is also a lack of comparative data for different antidote strategies. However, potential benefits of using the antidotes include tissue preservation and avoiding tissue necrosis. In developing the guidelines, we had an in-person roundtable discussion and weighed risks and benefits to ensure patient safety above all else. Brittany Harvey: I appreciate that description of the recommendation here. So then you just mentioned that there's a specific recommendation for paclitaxel and docetaxel. So what is recommended for those patients with extravasation of paclitaxel or docetaxel? Dr. Aparna Jotwani: So here, we conditionally recommended the specific use of hyaluronidase as the antidote. This was based on five studies that all used hyaluronidase as an antidote to lower the risk of tissue necrosis. In the studies included, with a subgroup of patients that experienced taxane-related extravasation, development of necrosis ranged from 0% to 0.83% among the patients who received an antidote. The potential harms associated with this were likely trivial. Brittany Harvey: Thank you for providing that recommendation as well. So then the next section of the guideline, Dr. Thomas, what does the expert panel recommend for use and duration of thermal compress? Dr. Tanya Thomas: So the expert panel actually recommends the use of thermal compresses, and the recommendations are based on the available literature for the various agents and the actual time frames most frequently used for the compress application. The utilization of a thermal compress is recommended for 15 to 20 minutes at a time for 3 to 4 times daily, at least for the first 48 to 72 hours after that extravasation occurs. The actual frequency and duration may vary based on the extent of the extravasation and the agent involved in that extravasation. The intent of the warm compress is to help disperse the agent and reduce the localized accumulation of the agent, whereas the cold compress, it actually helps prevent the dispersion or the spread of the agent while allowing the antidote to help neutralize that agent. Warm compresses are recommended for extravasations involving the vinca alkaloids, etoposide, oxaliplatin, and the taxanes - paclitaxel and docetaxel - only when coadministering the antidote hyaluronidase. The use of a cold compress is actually recommended for extravasations involving the anthracyclines, antimetabolites, alkylating agents, and taxanes when coadministration of the antidote hyaluronidase does not occur. Brittany Harvey: Understood. Those specific and actionable recommendations are really key for clinical practice. So then, following those recommendations, how does the guideline address escalation of care and surgical referral for patients with central line extravasation? Dr. Tanya Thomas: So this topic actually had a lot of discussion. And while there is not enough evidence to make strong recommendations, the expert panel recognized that surgical referrals should be considered in certain scenarios. Dr. Aparna Jotwani: We discussed that certain scenarios would include high-risk populations, such as patients that are receiving DNA-binding vesicants, those with high-volume estimated extravasation, and those with CTCAE grade 2, which would be erythema associated with symptoms such as edema, pain, induration, and phlebitis, or grade 3, which would be symptoms of ulceration or necrosis or concern for severe tissue damage, or grade 4, where you would have a life-threatening consequence extravasation, may have a greater likelihood of benefiting from surgical referral and/or escalation of care as deemed appropriate. Brittany Harvey: Great. And yes, it's really important to provide all of these recommendations that you've both just gone through, even when we're faced with very low evidence. So then, Dr. Thomas, in your view, what is the importance of this guideline, and how will it impact clinical practice? Dr. Tanya Thomas: So when extravasations occur in the clinical setting, members of the interdisciplinary team can be faced with barriers related to where to look for the information, how to find all the relevant information in one concise place, how to provide education to the patient about how to care for the site of extravasation in the home setting, and also when to escalate to specialized teams. This can actually cause some added stress and anxiety, and in certain circumstances, may lead to delays in efficient management. This guideline provides the resource clinicians have been looking for. It includes comprehensive recommendations for antineoplastic extravasations in one guideline while also providing a one-page algorithm with the key information regarding the management of the extravasations. This allows all levels of providers to have evidence-based recommendations regarding initial management of the extravasation, for instance, how to manage the infusion, key site assessment reminders, available antidotes, and the use of thermal compress; the required documentation, recommended follow-up scheduling, in addition to key aspects of the patient education. This type of guidance is not found in any other single document regarding antineoplastic extravasation. Having this document readily available at the point of care potentially can reduce time required for providers to search for management recommendations and also provide consistency in patient education and follow-up management scheduling. It reduces uncertainty within interdisciplinary teams and can help inform policy development for clinicians to approach extravasations with confidence. Brittany Harvey: Absolutely. I agree that this is an incredible resource for clinicians with the recommendations, the algorithm that you mentioned, and the supporting evidence that underpins these recommendations to really provide both efficient and effective care for patients. So beyond the impact for clinical practice, Dr. Jotwani, how will these guideline recommendations affect patients receiving antineoplastic treatment for cancer? Dr. Aparna Jotwani: Exactly. In addition to the clinical care team, we want to help and benefit our patients. So, oncology patients that experience extravasations are at risk for, aside of the side effects of tissue necrosis and infection, they also are at risk for delay of cancer treatment. In making these guidelines, we kept in mind the cost and the efforts for patients, additional visits that they could incur, additional time and supplies for care of the extravasation, as well as cost. Our guideline aims to provide an evidence-based approach to the care of oncology patients receiving antineoplastic intravenous therapy. While there are gaps in the data due to the nature of these events, based on careful literature review, these guidelines serve as a basis for quality, standardized oncology care during extravasation. Personally, I hope our graphics especially can be used across the systems to guide clinical care. Brittany Harvey: Definitely. We hope that these recommendations improve treatment and treatment outcomes for all patients receiving antineoplastic treatment for cancer. So then you've also just mentioned some gaps in the literature. So Dr. Thomas, I'd like to turn to you to wrap us up and ask, what are the outstanding questions for the management of antineoplastic extravasation? Dr. Tanya Thomas: Yes, that's a good question. Two of the main outstanding questions are related to the management of extravasations involving the novel agents and extravasations involving multi-agent regimens. The current literature regarding how to effectively manage the multi-agent regimens, for instance, there is no clear guidance for managing the extravasation for someone who is receiving a regimen that involves simultaneous administration of, let's say, a vinca alkaloid and an anthracycline. One of those agents requires a warm compress while the other requires a cold compress, and there are different antidotes for those two agents. Additionally, there has not been a lot of published information on the impact of extravasation of those novel agents like the antibody-drug conjugates. With the pace of the drug development, a subgroup of the guideline panelists actually are exploring case reports specific to novel agents to help inform some future work. Brittany Harvey: Yes, we'll look forward to learning more about how to address these ongoing issues and potentially impact guideline recommendations in the future as well. So I want to thank you both so much for your work to develop this incredibly important guideline, and thank you for your time today, Dr. Thomas and Dr. Jotwani. Dr. Aparna Jotwani: Thank you for the opportunity. Dr. Tanya Thomas: Yes, thank you. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines. I also encourage you to check out the companion episode on this guideline on the ONS podcast, available on Amazon Music, Apple Podcasts, Spotify, and YouTube Music. And finally, you can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Kathleen Horst, Dr. Rachel Jimenez, and Dr. Yara Abdou discuss the updated guideline from ASTRO, ASCO, and SSO on postmastectomy radiation therapy. They share new and updated recommendations on topics including PMRT after upfront surgery, PMRT after neoadjuvant systemic therapy, dose and fractionation schedules, and delivery techniques. They comment on the importance of a multidisciplinary approach and providing personalized care based on individual patient characteristics. Finally, they review ongoing research that may impact these evidence-based guidelines in the future. Read the full guideline, "Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline" at www.asco.org/breast-cancer-guidelines" TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-01747  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. Kathleen Horst, expert panel chair from Stanford University; Dr. Rachel Jimenez, expert panel vice chair from Massachusetts General Hospital; and Dr. Yara Abdou, ASCO representative from the University of North Carolina, authors on "Postmastectomy Radiation Therapy: An American Society for Radiation Oncology, American Society of Clinical Oncology, and Society of Surgical Oncology Clinical Practice Guideline." Thank you for being here today, Dr. Horst, Dr. Jimenez, and Dr. Abdou. Dr. Kathleen Horst: Thank you for having us. 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. Horst, Dr. Jimenez, and Dr. Abdou 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. Then to dive into the content that we are here today to talk about, Dr. Horst, could you start us off by describing what prompted the update for this joint guideline between ASTRO, ASCO, and SSO, and what is the scope of this 2025 guideline on postmastectomy radiation therapy? Dr. Kathleen Horst: Thank you. This joint guideline was last updated in 2016. Over the past decade, the treatment of breast cancer has evolved substantially. Newer systemic therapy regimens have increasingly personalized treatment based on tumor biology, and local therapy management has explored both the de-escalation of axillary surgery and more abbreviated courses of radiation therapy. Given these advances, it was important to revisit the role of postmastectomy radiotherapy in this modern era of breast cancer therapy. This updated guideline addresses four key questions, including postmastectomy radiation therapy after upfront surgery as well as after neoadjuvant systemic therapy. It also reviews the evolving role of various dose and fractionation schedules and optimal treatment techniques and dose constraints. Brittany Harvey: Excellent. I appreciate that background, Dr. Horst. So then, next, Dr. Jimenez, I would like to review the recommendations of this guideline across those four key questions that Dr. Horst just mentioned. So first, what does the panel recommend for PMRT for patients who received initial treatment with mastectomy? Dr. Rachel Jimenez: The panel provided pretty strong consensus that patients with positive lymph nodes or patients with large tumors involving the skin or the chest wall should receive postmastectomy radiation. However, the panel also recognized that the omission of postmastectomy radiation may be appropriate for select patients who have positive lymph nodes and have an axillary lymph node dissection if they have a low nodal burden and other favorable clinical or pathologic features. For patients without lymph node involvement at the time of surgery and no involvement of the skin or chest wall, postmastectomy radiation was not advised by the panel. Brittany Harvey: Understood. It is helpful to understand those recommendations for that patient population. Following that, Dr. Abdou, what are the key recommendations for PMRT for patients who received neoadjuvant systemic therapy before mastectomy? Dr. Yara Abdou: When we think about PMRT after neoadjuvant treatment, the key point is that the initial stage of presentation still matters a lot. So for example, if a patient comes in with more advanced disease, say a large primary tumor, like a clinical T4, or more extensive nodal disease, like an N2 or N3 disease, those patients should get PMRT, no matter how well they respond to neoadjuvant therapy, because we know it reduces the risk of recurrence and that has been shown pretty consistently. On the other hand, if there are still positive lymph nodes after neoadjuvant treatment, basically residual nodal disease, PMRT is also strongly recommended because the risk of local-regional recurrence is much higher in that setting. The gray area is the group of patients who start with a lower burden of nodal disease, such as N1 disease, but then become node negative at surgery. For those patients, we tend to individualize the decision. So if the patient is young or has triple-negative disease, or if there is a lot of residual disease in the breast even though the nodes are cleared, then radiation is probably helpful. But if everything has melted away with pCR in both the breast and the nodes, then it may be safe to omit PMRT in those patients. For patients with smaller tumors and no nodal involvement to begin with, like a clinical T1-T2 N0, if they are still node negative after neoadjuvant treatment, then PMRT is generally not recommended because their baseline recurrence risk is low. And finally, if the margins are positive and cannot be re-excised, then PMRT is recommended after neoadjuvant therapy. Brittany Harvey: Yes, those distinctions are important for appropriate patient selection. So then, Dr. Horst, we have just reviewed the indications for PMRT, but for those patients who receive PMRT, what are the appropriate treatment volumes and dose fractionation regimens? Dr. Kathleen Horst: The guideline addresses coverage of the chest wall and regional nodes with a specific discussion of the data regarding internal mammary nodal irradiation, which has been an area of controversy over many years. The guideline also reviews the data exploring moderate hypofractionation, or shorter courses of radiation therapy. The task force recommends utilizing moderate hypofractionation for the majority of women requiring postmastectomy radiation, which is likely to have a large impact on clinical practice. This recommendation is based on the evolving data demonstrating that a 3-week course of radiotherapy after mastectomy provides similar oncologic outcomes and minimal toxicity for most patients compared to the standard 5-week treatment course. Brittany Harvey: Thank you for reviewing that set of recommendations as well. So then, Dr. Jimenez, to wrap us up on the key questions here, what delivery techniques are recommended for treating patients who receive PMRT? Dr. Rachel Jimenez: So this portion of the guideline is likely to be most helpful for radiation oncologists because it represents the most technical part of the guideline, but we do believe that it offers some important guidance that has, to this point, been lacking in the postmastectomy radiation setting. So first, the panel recommends that all patients should undergo 3-dimensional radiation planning using CAT scan based imaging, and this includes contouring. So contouring refers to the explicit identification, using a drawing interface on the CAT scan imaging, by the radiation oncologist to identify the areas that are targeted to receive radiation, as well as all of the nearby normal tissues that could receive unintended radiation exposure. And we also provide radiation oncologists in the guideline with suggestions about how much dose each target tissue should receive and what the dose limits should be for normal tissues. Additionally, we make some recommendations regarding the manner in which radiation is delivered. So for example, we advise that when conventional radiation methods are not sufficient for covering the areas of the body that are still at risk for cancer, or where too high of a dose of radiation would be anticipated to a normal part of the body, that providers employ a technique called intensity modulated radiation therapy, or IMRT. And if IMRT is going to be used, we also advise regular 3-dimensional imaging assessments of the patient's body relative to the treatment machine to ensure treatment fidelity. When the treatments are delivered, we further advise using a deep inspiration breath-hold technique, which lowers the exposure to the heart and to the lungs when there is concern for cardiopulmonary radiation exposure, and again, that image guidance be used along with real-time monitoring of the patient's anatomy when those techniques are employed. And then finally, we advise that patients receiving postmastectomy radiation utilize a bolus, or a synthetic substance placed on the patient's skin to enhance radiation dose to the superficial tissue, only when there is involvement of the skin with cancer or other high-risk features of the cancer, but not for every patient who receives postmastectomy radiation. Brittany Harvey: Understood. And then, yes, you just mentioned that section of the guideline is probably most helpful for radiation oncologists, but I think you can all comment on this next question. What should all clinicians, including radiation oncologists, surgical oncologists, medical oncologists, and other oncologic professionals, know as they implement all of these updated recommendations? Dr. Rachel Jimenez: So I think one of the things that is most important when we consider postmastectomy radiation and making recommendations is that this is a multidisciplinary panel and that we would expect and encourage our colleagues, as they interpret the guidelines, to employ a multidisciplinary approach when they are discussing each individual patient with their surgical and medical oncology colleagues, that there is no one size fits all. So these guidelines are intended to provide some general guidance around the most appropriate techniques and approaches and recommendations for the utilization of postmastectomy radiation, but that we recognize that all of these recommendations should be individualized for patients and also represent somewhat of a moving target as additional studies, both in the surgical and radiation oncology realm as well as in the systemic therapy realm, enter our milieu, we have to adjust those recommendations accordingly. Dr. Kathleen Horst: Yeah, I would agree, and I wanted to comment as a radiation oncologist, we recognize that local-regional considerations are intertwined with systemic therapy considerations. So as the data evolve, it is critical to have these ongoing updates in a cross-disciplinary manner to ensure optimal care for our patients. And as Dr. Jimenez mentioned, these multidisciplinary discussions are critical for all of us to continue to learn and understand the evolving recommendations across disciplines but also to individualize them according to individual patients. Dr. Yara Abdou: I could not agree more. I think from a medical oncology perspective, systemic therapy has gotten much better with adjuvant CDK4/6 inhibitors, T-DM1, capecitabine, and immune therapy. So these are all newer adjuvant therapies, so the baseline recurrence risks are lower than what they were in the trials that established PMRT. So the absolute benefit of radiation varies more now, so smaller for favorable biology but still relevant in aggressive subtypes or with residual disease. So it is definitely not a one-size-fits-all. Brittany Harvey: Yes, I think it is important that you have all highlighted that multidisciplinary approach and having individualized, patient-centric care. So then, expanding on that just a little bit, Dr. Abdou, how will these guideline recommendations affect patients with breast cancer? Dr. Yara Abdou: So basically, reiterating what we just talked about, these guidelines really move us towards personalized care. So for patients at higher risk, so those with larger tumors, multiple positive nodes, or residual nodal disease after neoadjuvant therapy, PMRT remains essential, consistently lowering local-regional recurrence and improving survival. But for patients at intermediate or lower risk, the recommendations support a more selective approach. So instead of a blanket rule, we now integrate tumor biology, response to systemic therapy, and individual patient factors to decide when PMRT adds meaningful benefit. So the impact for patients is really important because those at high risk continue to get the survival advantage of radiation while others can be spared the unnecessary treatment and side effects. So in short, we are aligning PMRT with modern systemic therapy and biology, making sure each patient receives the right treatment for their situation. Brittany Harvey: Absolutely. Individualizing treatment to every patient will make sure that everyone can achieve the best outcomes as possible. So then, Dr. Jimenez, to wrap us up, I believe Dr. Horst mentioned earlier that data continues to evolve in this field. So in your opinion, what are the outstanding questions regarding the use of PMRT and what are you looking to for the future of research in this space? Dr. Rachel Jimenez: So there are a number of randomized phase III clinical trials that are either in active accrual or that have reported but not yet published that are exploring further de-escalation of postmastectomy radiation and of axillary surgery. And so we do not yet have sufficient data to understand how those two pieces of information integrate with each other. So for example, if you have a patient who has a positive lymph node at the time of diagnosis and forgoes axillary surgery aside from a sentinel lymph node biopsy, we do not yet know that we can also safely forgo radiation entirely in that setting. So we expect that future studies are going to address these questions and understand when it is appropriate to simultaneously de-escalate surgery and radiation. Additionally, there is a number of trials that are looking at ways in which radiation could be omitted or shortened. So there is the RT CHARM trial, which has reported but not yet published, looking at a shorter course of radiation. And so we do make recommendations around that shorter course of radiation in this guideline, but we anticipate that the additional data from the RT CHARM study will provide further evidence in support of that. Additionally, there is a study called the TAILOR RT trial, which looks at forgoing postmastectomy radiation in patients who, to Dr. Abdou's point, have a favorable tumor biology and a low 21-gene recurrence score. And so we are going to anticipate the results from that study to help guide who can selectively forgo postmastectomy radiation when they fall into that favorable risk category. So there are a number of questions that I think will help flesh out this guideline. And as they publish, we will likely publish a focused update on that information to help provide context for our colleagues in the field and clarify some of these recommendations to suit the latest data. Brittany Harvey: Absolutely. We will look forward to those de-escalation trials and ongoing research in the field to build on the evidence and look for future updates to this guideline. So I want to thank you for your work to update these guidelines, and thank you for your time today, Dr. Horst, Dr. Jimenez, and Dr. Abdou. Dr. Rachel Jimenez: Thank you. Dr. Yara Abdou: Thank you. Dr. Kathleen Horst: Thank you. Brittany Harvey: And then finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Cris Bergerot and Dr. Enrique Soto join the podcast to discuss the new global guideline on geriatric assessment. This guideline provides evidence-based, resource-stratified recommendations across the basic, limited, and enhanced settings. Dr. Bergerot and Dr. Soto discuss who should receive a geriatric assessment, the role of geriatric assessment, which elements of geriatric assessment can help predict adverse outcomes, and how a geriatric assessment is used to guide care and make treatment decisions. They comment on the importance of this guideline worldwide, and the impact of this guideline for a wide range of clinicians, patients, researchers, policymakers, and health administrators.   Read the full guideline, "Geriatric Assessment: ASCO Global Guideline" at www.asco.org/global-guidelines." TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/global-guidelines. Read the full text of the guideline, view clinical tools and resources, and review authors' disclosures of potential conflicts of interest in the JCO Global Oncology,       https://ascopubs.org/doi/10.1200/GO-25-00276       Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Cris Bergerot from OncoClínicas & Co and Dr. Enrique Soto from the University of Colorado, co-chairs on "Geriatric Assessment: ASCO Global Guideline". Thank you for being here today, Dr. Bergerot and Dr. Soto. Dr. Cris Bergerot: Thank you. Dr. Enrique Soto: Thanks for the invitation, Brittany. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Bergerot and Dr. Soto who have joined us here today, are available online with the publication of the guideline in JCO Global Oncology, which is linked in the show notes. So then to jump into the guideline here, Dr. Soto, could you start by providing an overview of the scope and the purpose of this global guideline on geriatric assessment? Dr. Enrique Soto: Of course, Brittany. So, this guideline comes from a request from the global oncology community and from the geriatric oncology community, who is very interested in making sure that geriatric oncology recommendations that are used in the United States can be adopted and used globally. So, this was a very highly rated topic when we had our call for proposals for guidelines, and that's why we decided to do this. The idea of this guideline is to provide resource-stratified recommendations for the use of geriatric assessments and interventions in older adults with cancer across different settings, right? And that these guidelines can be applied by clinicians working in low- and middle-income countries, but also, in a way, by clinicians working in community settings where the availability of resources may be limited. And the idea of these recommendations is to help clinicians evaluate older people with cancer better and also understand which interventions can be implemented with the resources they have and which interventions have a bigger bang for the buck, so to speak. And as all evidence-based, stratified guidelines that ASCO conducts, we stratified resources as basic, limited, or enhanced. And that means resources that go from those that provide the greatest benefits for patients in terms of outcomes to those that are evidence-based but provide additional additive benefits. And those resource-stratified recommendations can be found in the ASCO website as to how these guidelines are developed, and that's pretty standard for most resource-stratified guidelines. Brittany Harvey: Great. I appreciate that background and the impetus for this guideline, and thank you for providing that resource-stratified framework of basic, limited, and enhanced. I think that helps provide context for the guideline recommendations here. So then, Dr. Bergerot, I'd like to next review the key recommendations of this guideline across the four clinical questions that the guideline addresses. So, across those settings, the basic, limited, and enhanced settings, what is the role of geriatric assessment in older adults with cancer to inform specific interventions? Dr. Cris Bergerot: I think this is one of the most important points, so let's break it down. First off, who should actually receive the geriatric assessment? And the recommendation is clear. All patients aged 65 and older who are being considered for systemic cancer therapy should undergo a geriatric assessment. Now, depending on the available resources, for example, in basic setting, a quick screening may be enough, but in enhanced setting, a comprehensive geriatric assessment is encouraged. And for our next question, in which elements of the geriatric assessment can help predict poor outcomes, the core domains to focus on include things like physical function, comorbidities, polypharmacy, cognition, nutrition, social support, and psychological health. And there are also validate tools like the G8, the CGA, and the CARG that can be used depending on the setting and resources available. Now, talking about how we actually use the geriatric assessment to guide care, the assessment results can guide interventions to reduce treatment-related toxicities and maintain the patient functions. So, even in basic settings, the result can help guide those adjustments or identify the need for supportive care. And in more resource settings, we can implement more tailored intervention based on those findings. And finally, for our fourth question: How can geriatric assessment help guide treatment decisions? So, GA can influence decisions about how aggressive treatment should be, help clarify goals of care, and determine whether a curative or palliative approach makes the most sense. And again, even in settings with limited resources, a simplified GA can still provide meaningful guidance. Brittany Harvey: Great. Thank you, Dr. Bergerot, for that high-level overview of the recommendations of this guideline. So then, following that, Dr. Soto, which geriatric assessment tools and elements should clinicians use to predict adverse outcomes for older patients receiving systemic therapy across the basic, limited, and enhanced settings? Dr. Enrique Soto: Yeah, so that is an excellent question because it's something that people want to know, right? When people start developing a geriatric oncology clinic, one of the first things they want to know is which tools should I use. And we hope that this guideline will provide some clarity regarding this. So, our overarching recommendation is that every patient, regardless of the level of resources, should receive some sort of geriatric assessment. And that geriatric assessment can go from a simple screening tool, such as the G8 tool, which is available online and very easy to do, and that can be done in basic settings, to a more sophisticated geriatric assessment. The important thing, and what we emphasize in the guideline, is that regardless of the tool you use, it should include those high-priority domains that are associated with outcomes in older adults with cancer. And those include an assessment of physical function, of cognition, emotional health, comorbidities, polypharmacy, nutrition, and social support. In addition to that, an important thing that the guideline does is endorse the recommendation from our parent guideline, the guideline from high-income settings, the practical geriatric assessment, which is a tool that was actually developed by the ASCO Geriatric Oncology Group, which is a self-administered tool that people can use to evaluate their patients in a prompt and fast manner. And what we actually did for this guideline is include the validation of the various tools included in the practical geriatric assessment in the five most widely spoken languages in the world, including Hindi, Chinese, Spanish, and French, and Portuguese. And so, most of these tools are validated in these languages. So, we believe that the practical geriatric assessment is a tool that can be utilized across settings and that doesn't require a lot of resources. I think an important future step is making sure that we get the practical geriatric assessment translated into various languages, and we're working with the ASCO team in getting that done. Brittany Harvey: That's an excellent point. And yes, we'll hope to have the practical geriatric assessment translated into more languages. And that tool is available linked in the guideline itself, and we'll also provide a link for listeners in the show notes of this episode (Practical Geriatric Assessment). So then, following that, Dr. Bergerot, in resource-constrained settings, what general life expectancy data should clinicians use to estimate mortality and inform treatment decision-making? Dr. Cris Bergerot: So, in basic and limited resource environments, you might not have access to every tool or specialist, but you can still make informed and thoughtful decisions. So, what the guideline recommends is to start with population-level life expectancy tables. These are available through the WHO Global Health Observatory, and they offer useful starting points. And if available, clinicians should also look for country-specific or regional survival data. That kind of local information can be even more relevant to your patient population. The clinical judgment is also key here, and it becomes even more powerful when it's guided by the patient's geriatric assessment results. And when possible, use age- and comorbidity-adjusted models, like the Lee index or tools from the ePrognosis. This can help refine estimates of mortality risk and also inform how aggressive treatment should be. Brittany Harvey: Absolutely. I appreciate you providing those specifics as well. So then, following that, Dr. Bergerot mentioned this a little bit earlier, but Dr. Soto, how should geriatric assessment be used to guide management of older patients with cancer across the basic, limited, and enhanced settings? Dr. Enrique Soto: Yeah, and again, that's another important focus, right? Because if we assess things and then don't do anything about them, then why even assess them, right? And in many settings, people say, "Well, I don't have the tools to provide the interventions that these patients actually need." And a very significant part of building this guideline was coming up with a resource-stratified and evidence-based way in which to prioritize which interventions provide most benefits for older adults with cancer. And so, for each level and each domain, we have a series of interventions that have been stratified according to importance and evidence base, and that is actually one of the coolest features of the guideline. We included a table, and then we have for each of the domains, including falls, functional status, weight loss, et cetera, what are the interventions that oncologists can do in their clinical visit without needing a lot of resources, including providing some specific information, giving some recommendations to patients, to more high-level things that can be done when the healthcare system allows it, such as working with a nutritionist, providing supplements, testing for particular cognitive impairments, et cetera. So, I encourage people to take a look at that table. It was really a lot of work putting that table together, and that table has specific recommendations for each setting, and I think people will find it very useful. Brittany Harvey: Absolutely. That table certainly contains a lot of information that's very helpful for clinicians. I think it's important to call out those tailored interventions to improve care and quality of life for every patient. So then, we've just reviewed all of the recommendations in this guideline. So, I'd like to ask you, Dr. Bergerot, in your opinion, what should clinicians know as they implement these recommendations across resource levels? Dr. Cris Bergerot: I would say that clinicians should remember that even a brief geriatric assessment can make a meaningful difference. You don't need a full suite of tools to improve quality of care, but clinicians should tailor all the tools that are available in their local context and always keeping in mind the core geriatric domains that we have mentioned in the very beginning of our podcast. And let's be clear, the goal of the assessment isn't just to gather data, as Enrique mentioned; it's to use this information to guide treatment decision and also to improve outcomes. And whenever possible, clinicians should engage interdisciplinary teams that might include nurse, psychologist, social workers, community health workers, or anyone who can help address the patient's broader needs. And flexibility really matters. So, especially in settings with limited access to specialists or diagnostics, we should prioritize what is feasible and what will truly help our patients during their journey. And above all, we should keep this in mind that equity in care delivery is essential. Just because resources are limited doesn't mean we can't deliver age-sensitive and even patient-centered care. Brittany Harvey: Definitely. That multidisciplinary care that you mentioned is key, and also thinking about what is feasible across every resource level to provide optimal care for every single patient. So then, to expand on that just a little bit and to wrap us up, Dr. Soto, what is the impact of this guideline for older adults with cancer globally? Dr. Enrique Soto: Well, what we hope this guideline will lead to is to a boom in geriatric oncology worldwide, right? That is our final goal. And what we want is for clinicians interested in starting a geriatric oncology program or setting up a geriatric oncology clinic to use these guidelines in order to justify the interventions that they're going to do, to pick the important partners they need for their multidisciplinary team, to choose the tools that they're going to implement. And then, with that, to present this to leaders in their hospitals, leaders in their healthcare system so that they can start these clinics that will ultimately lead to better outcomes for older adults with cancer. So, I encourage people to view this as high-quality, evidence-based recommendations that are done by a group of experts and with a thorough review of the literature and also based on our parent guidelines. The fact that these guidelines are resource-stratified does not by any mean signify that they're of less quality or that the recommendations that are included in those are not proven to improve outcomes, cancer-specific and also general outcomes, in older adults with cancer. Another thing that I think these guidelines could do in the future is motivate researchers in low- and middle-income countries to fill in the gaps that we have identified in these guidelines. We've made it very clear across the guidelines where evidence is lacking. And I think that this should prompt researchers across the globe to start trying to fill in these gaps with high-quality research. And finally, I also think that this is a call for policymakers, health administrators, and people interested in public health to start scaling up resources so that places with basic resources can eventually become places with more sophisticated resources. And I think this does not only apply to low- and middle-income countries, but also to community oncologists in the US who may be facing resource constraints. And I think that these guidelines can help them stratify and understand what things should be implemented first and how to scale up. So yeah, that's the dream that with this guideline, more people will start implementing geriatric oncology around the globe and that ASCO will continue to be a leader in setting the stage for what should be done in geriatric oncology and for improving care to older adults with cancer, regardless of where they live. Brittany Harvey: Absolutely. This guideline is wide-reaching and has important impacts worldwide. So, I want to thank you both so much for the huge amount of work you took to develop this evidence-based guideline, and thank you for joining me on the podcast today, Dr. Bergerot and Dr. Soto. Dr. Cris Bergerot: Thank you so much. Dr. Enrique Soto: Thank you for the invitation. It was a pleasure. Brittany Harvey: And finally, thank you to our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/global-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've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Ms. Kim Woofter and Dr. John Cox discuss the latest updates to the evidence-based standards on oncology medical homes developed by ASCO and COA. These standards serve as the basis for the ASCO Certified program. They share the new and revised standards around topics including the culture of safety and just culture in oncology practice, geriatric assessment and geriatric assessment-guided management, and multidisciplinary team management. They expand on the importance of these standards for clinicians and oncology practices to ensure every patient receives optimal care. Read the complete standards, "Oncology Medical Homes: ASCO-Community Oncology Alliance Standards Update" at www.asco.org/standards. TRANSCRIPT These standards, clinical tools, and resources are available at www.asco.org/standards. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the JCO Oncology Practice, https://ascopubs.org/doi/10.1200/OP-25-00498 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Ms. Kim Woofter, a registered nurse in practice leadership and administration from AC3 Inc in South Bend, Indiana, and Dr. John Cox, a medical oncologist and adjunct faculty member from UT Southwestern Medical Center in Dallas, Texas, co-chairs on "Oncology Medical Homes, American Society of Clinical Oncology – Community Oncology Alliance Standards." Thank you for being here today, Ms. Woofter and Dr. Cox. Dr. John Cox: You bet. Ms. Kim Woofter: Thank you. Brittany Harvey: And then before we discuss these standards, I'd just like to note that ASCO takes great care in the development of its standards and ensuring that the ASCO Conflict of Interest Policy is followed for each guidance product. The disclosures of potential conflicts of interest for the expert panel, including Dr. Cox and Ms. Woofter, who have joined us here today, are available online with the publication of the standards in JCO Oncology Practice, which is linked in the show notes. So then, to dive into what we're here today to talk about, Dr. Cox, could you start us off by explaining what prompted an update to these ASCO-COA standards and what the scope of this update is? Dr. John Cox: Well, the ASCO-COA standards relative to defining and outlining Oncology Medical Home were initially published four or five years ago. At the time, we planned a regular update of the standards. So, in essence, this is a planned update. The whole program is built on the idea of continuous improvement. So, this update and future updates are prompted and defined by our literature, our science, the science of care delivery, and new developments and insights gained from studies and evaluations of care delivery methods, and informed by the practice. These standards are in place to underpin a program of care delivery by ASCO, the ASCO Certified, and as practices engage in this program, we are learning from them. The whole idea is to enlarge and improve how patients are cared for in practice. Brittany Harvey: Absolutely. It's great to have this iterative process to continue to review the evidence and update these standards that form the basis for ASCO Certified. So then, following that background, Ms. Woofter, I'd like to review the key points of the revised standards for our listeners. First, how do the revised standards address the culture of safety and just culture in oncology practice? Ms. Kim Woofter: I think safety is of utmost importance to all of us. So let me say that first and foremost. And what we know in oncology is our QOPI standards already address safety in the infusion suite process. So, safe delivery of chemotherapy agents and antineoplastics. It also talked about near misses and medication errors - absolutely essential, for sure. But what we need to do is look at a more systemic approach to safety because we know is processes throughout an organization they'll often cause you trouble. To do that, we know you need what we call a just culture, which is a very common term in today's workplace. But what it really means is it's a culture of open reporting of any potential for error, any potential for malfunction, and it can be in any place in the organization. So, what we are doing in our new standard is to say, look at your entire processes throughout the organization, and approach that in an open-minded way so that people don't feel scared to report things, and it's a really positive approach to intervening early and making sure that errors don't occur anywhere in the workplace. Brittany Harvey: Taking that systemic approach to look at overarching processes seems really key to ensuring safety in oncology practices. So then, the next new section, Dr. Cox, what are the new OMH standards surrounding geriatric assessment and geriatric assessment–guided management? Dr. John Cox: This is a challenging update for our standards. As many folks in practice recognize, there is a deep literature on recognizing the geriatric population in oncology. Geriatric - those in my age group over age 60, 65 - make up the majority of cancer patients in this country. And yet, there are many aspects that should be taken into account as you address treatment decisions in this population. ASCO's recognized this. There has been a guideline previously on geriatric assessment. It's been updated, and we really felt it's time that it be incorporated in any iteration of what oncology care delivery means, so, within the oncology medical home standards. In short, what the standard outlines is that practices that are using these standards, that are using this benchmark, should have a geriatric assessment for patients within the practice care and use that information to guide management. Now, the standard allows wide exploration of how practices meet this standard, but it really puts on the table that if an oncology practice in the United States, or anywhere in the world really, is adhering to a good practice, that they're going to include and recognize these assessments in practice. Ms. Kim Woofter: I would like to add that this is a highly discussed and reviewed standard. Many of our community practices were concerned that they would have the time and manpower to perform this assessment. We all know it reduces toxicities if done appropriately at treatment planning, and so the outcomes are better. And we really left it to the practices to define how they're going to implement it, understanding that it will evolve to every single patient, but maybe day one, it was a step approach to be able to implement. So, I was really proud of the team that - the expert panel - that said, okay, let's step into this, but we do think it's essential. Brittany Harvey: Absolutely. It's important to recognize that practices may have limited resources and time, and implementing it in the way that makes sense for them allows this to be a standard that can be used in practice. And it's great to have this geriatric assessment guideline integrated into these standards to improve care delivery. And we can provide a link to that guideline in the show notes of this episode as well (Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update). So then, following that section of the standards, Ms. Woofter, how do the updated standards now address multidisciplinary team management? Ms. Kim Woofter: Well, we address multidisciplinary team management in a more comprehensive way in the updated standard. We always thought that that was a critical piece when doing treatment planning, and we kind of highlighted it in a bigger way, understanding that not everybody has the same resources available at the time of treatment planning. And again, this was a much-discussed standard, in that that multidisciplinary team approach doesn't necessarily have to be in a tumor board or a prospective analysis of every case. It is actually a conversation between specialists, between the surgeon and pathologist and the medical oncologist. And we are saying, do what works for you, but we know that that team approach, every specialty coming to the table at time of treatment planning, truly provides better outcomes for our patients. And so we kind of reiterated that, understanding that again, it doesn't have to be a formal tumor board, but it has to be a dialogue between specialties. And we highlighted that again in the new standard. Brittany Harvey: Open communication of all team members is really critical to providing optimal care. Dr. Cox, I'd like to ask you, in your view, how will these updated standards impact both clinicians and oncology practices? Dr. John Cox: Well, our whole goal with discussing a comprehensive care model for oncology practice is to have a benchmark, to have an iteration of what good oncology care delivery looks like. So, our hope is that practices, all practices, whether you're participating formally in ASCO Certified, the marquee quality program for ASCO, or if you are simply running a practice or a team within an academic environment or institutional environment, these standards are to apply across the board wherever oncology is practiced - that you can look at these standards as a benchmark and compare what you are doing in your practice and where are the gaps. So ideally, we drive improved care across the board. You know, one thing I've learned over the last couple of years as ASCO Certified is getting spun up and using and implementing these standards, is practices are remarkably innovative. We've learned a lot by seeing how pilot practices have met the standards, and that's gone into informing how we can improve care delivery for all of our practices and, importantly, for the team members who are delivering this care. The fourth rail of burnout and the like is inefficiency that occurs in practice. And when you know you've got a good, spun-up, effective team, less burnout, less stress for practice. I hope clinicians and oncology practices will use this to help drive improvements in their care and gain insight into how they can approach practice problems in a better way. Kim, you've been leading practices. I have to ask you, your thoughts in leaning into this question. Ms. Kim Woofter: I think very well said, I will say that first. And what I love about this is for practice leaders who are new to our ecosystem, if you will, they need a playbook. It's "Where do I begin?" And Dr. Cox said it very well, no one does everything perfectly day one, but it's a step-by-step self-assessment approach to say, "How do I get to this gold standard?" I really love the standards because they are very comprehensive, everything from treatment planning to end of life. So it's the spectrum of the care we deliver in the oncology setting. So as a leader and an administrator, it is the standard I want all of my departments to understand, adhere to, and engage, and be excited about. We now have a baseline approach, and what's even more important, these standards will evolve as our intelligence evolves, as literature evolves. It's a system that will always grow and change, and that's what we love about it. It's not a one-and-done. So, I'm very proud of the fact that it gives them a road map. Brittany Harvey: Yes, these evidence-based standards provide a critical foundation for practices in ASCO Certified, for those team members you mentioned, and for quality improvement beyond just those individuals and practices as well. So then finally, to wrap us up, Ms. Woofter, what do these revised standards mean for patients receiving cancer treatment? Ms. Kim Woofter: Well, I think that's the most exciting part, is we all do this for our patients and the best outcomes for our patients and the best treatment plans for our patients and their families. And these standards, that is their core, their absolute core. So what it's going to do for a patient is they can say, "Am I at a practice that implements ASCO standards?" And if that is a 'yes', there's a confidence that, "I am in an evidence-based medicine thinking practice, I have a team around me, they will care for me not only at time of treatment planning but at the time of end of life, they will help me be part of that decision-making, and they will give me resources available to me in my community." So, it is a true comprehensive approach. As a patient, I have that comfort, that it is bigger than just a great doctor. It is a great team. As a patient, that would be very important to me and important to my family. That being said, Kim Woofter would love every practice to be ASCO Certified. Understanding that that isn't feasible day one, just to know that the practice is implementing and engaging the standards is the great place to start. Every patient can't go to an ASCO Certified practice day one, but our dream would be that everyone would adhere to those standards, engage those standards, believe them, educate their staff on what they mean, so that patient outcomes and satisfaction will be optimized for everyone. The other piece to this that we all know is if you give evidence-based medicine, cost-effective, efficient care, it's better for the system as a whole. And I'm not saying that insurance is our driver - certainly patient outcomes are our driver - but the whole ecosystem of oncology benefits when you do the right thing. Dr. John Cox: It's hard to add anything to Kim's good statements, but I just highlight that this whole area began with the patient-centered medical home, and every time we've met, patients and how we deliver care to patients is top of mind. I think that reflects our community. It reflects oncology as a whole. I don't know any oncologist or practice that is focused on anything else as the prime goal. Brittany Harvey: That's what I was just going to say. The ultimate goal here is to provide patient-centered care across where every single patient is receiving treatment and at every stage of that treatment. So, I want to thank you both so much for your work to update these standards, to review the evidence, and discuss with the experts on the panel to come up with the solutions that will help drive quality improvement across care delivery. So, thank you for that, and thank you for your time today, Dr. Cox and Ms. Woofter. And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the complete standards, go to www.asco.org/standards. You can also find many of our standards and interactive resources in the free ASCO Guidelines app, which is available on the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Joshua Reuss joints that podcast to discuss the latest changes to the living guideline on stage IV NSCLC with driver alterations. He discusses the new evidence for NSCLC with EGFR mutations and NRG1 fusions and how this impacts the latest recommendations from the panel. He shares ongoing research that the panel will review in the future for further updates to this living guideline, and puts the updated recommendations into context for clinicians treating patients with stage IV NSCLC. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-01061 Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1." It's great to have you here today, Dr. Reuss. Dr. Joshua Reuss: Thank you. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Reuss, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So to dive into what we're here today to talk about, Dr. Reuss, this living clinical practice guideline for systemic therapy for patients with stage IV non–small cell lung cancer with driver alterations is updated on an ongoing basis. So what prompted this latest update to the recommendations? Dr. Joshua Reuss: Yes, thank you. It's very important that we have living guidelines that are continuously updated. We obviously don't live in a static environment where things are non-changing, and we really need to apply the most up-to-date and current evidence to treat our patients with the most effective strategies, the most groundbreaking strategies. And so to have guidelines that can be disseminated, particularly these ASCO guidelines, to treating providers is incredibly important. So, with any of these updates, we review ongoing studies, published work, for the quality of evidence to see if it's something that warrants making adjustments to our guidelines or at least incorporating the information so that providers can review it and incorporate this into their own personal decision-making. So in this particular update, we reviewed evidence particularly pertaining to EGFR-mutated non–small cell lung cancer and non–small cell lung cancer harboring an NRG1 fusion. Brittany Harvey: Yes, certainly there's a lot of new evidence in the advanced non–small cell lung cancer field, and so we appreciate the panel's continuous review of this evidence. So then you just mentioned two separate areas where the panel reviewed new evidence. So starting with that first one, what updated evidence did the panel review on first-line treatment options for patients with EGFR alterations, and how did this impact the recommendations? Dr. Joshua Reuss: Yes, so advanced EGFR-mutated non–small cell lung cancer, at least with classical activating alterations - that is our exon 19 deletions and our exon 21 L858R mutations - is something that's really evolved rapidly in the last few years. You know, for many years, we basically, for the frontline treatment setting, were saying, "Okay, we have a targeted therapy, osimertinib. We're going to give that, and we're going to see what effect we can get out of that," with, you know, a median time of duration of treatment response averaging around 18 months, knowing that there are some that that's a lot longer and some that are a lot shorter. But recently, we've seen a lot of data emerging on combination strategies. The guideline has already been updated to incorporate two of these combinations: osimertinib with chemotherapy based off of the FLAURA2 trial, and then the combination of amivantamab with lazertinib based off of the MARIPOSA trial. And that was data on progression-free survival that was published and led to those particular recommendations. Now, more recently, we've seen data come out in smaller, randomized studies for other combinations. And more recently, we reviewed the RAMOSE study. So this was a phase II, open-label, randomized trial for patients with tyrosine kinase inhibitor–naive and really, treatment-naive advanced EGFR-mutated non–small cell lung cancer harboring one of these two classical EGFR alterations, randomized to either osimertinib alone or osimertinib with the combination of ramucirumab, which is an anti-VEGF agent. There's been a lot of data, preclinical and clinical, for the role of VEGF blockade, particularly in EGFR-mutated non–small cell lung cancer, so exploring the combination of this for synergy in the frontline setting really made a lot of sense. So again, this was a phase II trial that randomized patients prospectively to one of these two regimens. The population here is really what we typically see with EGFR-mutated non–small cell lung cancer, predominantly a younger population - median age on this study was 65 - predominantly female - 71% female - and predominantly nonsmokers. Now, what this study showed was that at a median follow-up of 16.6 months, the progression-free survival favored the combination arm with a median progression-free survival of 24.8 months with the combination of osimertinib plus ramucirumab versus 15.6 months for osimertinib alone, for a hazard ratio of benefit of 0.55. The landmark one- and two-year endpoints for progression-free survival also favored the combination arm, and response rates were relatively comparable between groups, with overall adverse events being more frequent in the combination group, specifically high blood pressure, proteinuria, and epistaxis, which are our common adverse events related to VEGF-blocking agents. So, it's good to see data in this space. Now, of note, though, this was a phase II study, so not a phase III level of evidence. In addition, when looking at the population, this was a randomized, multicenter study, but it was a US-only population. There was also some imbalance in the number of visits between arms, so the combination arm was seen more frequently than the arm that got osimertinib alone. Now, the imaging assessments were no different, but obviously this could lead to potential confounding, at least in timing of awareness of potential side effects and and things being brought to the attention of investigators. So very promising data here, but because, you know, of this being a phase II study, this actually led to no changes in the guideline at this time. Brittany Harvey: Understood. Yes, as you mentioned prior, it's important to understand the full body of evidence and to review the trials even when it doesn't impact the recommendations. Dr. Joshua Reuss: And I will say that, you know, there is an ongoing phase III study looking at a very similar combination. It's the phase III ECOG-ACRIN trial of the combination of osimertinib plus bevacizumab versus osimertinib alone in this specific population. So, you know, I think we will see phase III–level data for a combination of VEGF with osimertinib, but again, promising phase II data that did not lead to a change in the recommendation at this time. Brittany Harvey: Absolutely. We'll look forward to that ongoing trial to learn more about combination in this patient population. So then moving to that second patient population that you mentioned earlier where the panel reviewed evidence, what is the updated evidence and recommendation for patients with NRG1 fusions? Dr. Joshua Reuss: Yeah, so this was an exciting update that we made more recently with this unique iteration of the living guidelines. So, NRG1 fusions, this is perhaps a newer kid on the block in terms of driver alterations that has been known to be identified in non–small cell lung cancer among other solid tumors. It is very rare, occurring in less than 1% of solid tumors, but something that we know is a unique oncogenic pathway that can lead to oncogenesis and cancer development, including in non–small cell lung cancer. So up until now, unfortunately, there have not been targeted therapies that target this unique alteration. It's somewhat different than other driver alterations where there's a top-level signaling change in a protein. This is more of a ligand alteration that then alters, that then enables activation of more classical pathways, but again, through upregulation of a unique ligand. So a slightly different pathway but something that we know should be able to be targeted to promote patient survival for those with NRG1 fusions. So the therapy here is a therapy called zenocutuzumab. It's an IgG1 bispecific antibody against HER2 and HER3. So it prevents the downstream dimerization and signaling that occurs as a result of this NRG1 fusion and upregulation of the NRG1 signal. This was, as you can imagine with a rare alteration, a large phase II registrational study that examined this in advanced solid tumors containing the NRG1 fusion. This is the NRG1 registrational trial. And this study enrolled patients with advanced solid tumors who had progressed on prior therapy. Patients were treated with zenocutuzumab 750 milligrams IV every two weeks. Among 158 response-evaluable solid tumor patients, the response rate was 30%, median duration of response of 11.1 months, and a median progression-free survival of 6.8 months. Now, in those with non–small cell lung cancer, that made up 93 response-evaluable patients, very similar outcomes there: a response rate of 29%, median duration of response of 12.7 months, and a median progression-free survival of 6.8 months. This therapy did appear to be well tolerated. The most common higher-grade emergent side effects - grade 3 or higher - were anemia occurring in 5% and elevated liver numbers occurring in 3%. So this is a subsequent-line study, so this led to the updated recommendation that clinicians may offer zenocutuzumab in the subsequent-line setting for patients with advanced non–small cell lung cancer who harbor NRG1 fusions. So I think this does speak toward the incredible importance of next-generation sequencing and molecular testing for patients, particularly to include testing that looks at the RNA. These large fusions can sometimes be very challenging to detect on DNA sequencing platforms alone, so it's important to, if you have a high level of suspicion for an alteration like this, perhaps some of the mucinous adenocarcinomas where it's been challenging to find a driver alteration, and it's someone who is a never-smoker, really would want to include molecular testing that assesses the RNA level and not just the DNA. Brittany Harvey: Absolutely. It's important to have all the biomarkers available so that clinicians are able to use that to inform their decision-making. So then, given these changes in the guideline, what should clinicians know as they implement this latest living guideline update? And how do these changes impact patients? Dr. Joshua Reuss: Yeah, I think talking in reverse order of what we just discussed here, there is a new guideline update for NRG1 fusions. So I think making sure that that's being evaluated, that clinicians are testing for that and really looking for that result that should be incorporated in in most next-generation large sequencing assays to get that result, but it's very important that that is not overlooked now that we do have a therapy that's available in the subsequent-line setting, though it is important to note that patients with NRG1 fusions, at least the limited data that there is suggests that the efficacy to standard chemoimmunotherapy regimens is overall poor. So physicians unfortunately might be facing this question for second-line therapy in patients with NRG1 fusions sooner rather than later. For the former, for EGFR-altered non–small cell lung cancer and how do we incorporate VEGF-containing regimens into these patients? Our guideline top-level update did not change based off of review of this new study, but it's important for clinicians to know what other combinations may exist. You know, there are phase III studies looking at this combination in the frontline setting. And of course, there is data on other bispecific molecules that incorporate VEGF in the subsequent-line setting, particularly a combination that includes the VEGF/PD-1 bispecific antibody ivonescimab that's being studied in the HARMONi-A trial for patients with EGFR-mutated advanced non–small cell lung cancer, for which we hope to get some more definitive data in the coming months. Brittany Harvey: Definitely. And then you've just mentioned a few ongoing trials where we're looking for evidence to inform future updates. But thinking beyond that, into the future, what is the panel examining for future updates to this living guideline? Dr. Joshua Reuss: It's a very exciting time to be in the world of treating advanced non–small cell lung cancer, particularly patients with driver alterations, because there is so much evolving data that's changing our practice in real time, again highlighting the importance of these living guideline updates. I'd say there's many things that we're excited to see. You know, a lot of the combination regimens in EGFR-mutated non–small cell lung cancer for which there are approvals and current recommendations in our guideline, particularly osimertinib plus chemotherapy and amivantamab plus lazertinib - those are the two approved combination strategies in the front line - we are now seeing the emergence of overall survival data for those combinations. So obviously that is something that's going to be very important for the committee to review and incorporate into guideline updates. There are several new therapies coming down the road for other driver populations. We recently saw an approval for taletrectinib for ROS1 fusion–positive non–small cell lung cancer, so it's going to be important that the committee reviews the data and the publications regarding that therapy. And then there are other novel therapies that we're looking to see updated data on. There are multiple antibody-drug conjugates, which take the potent power of a chemotherapy molecule and attempt to make that targeted with an antibody targeting to a unique feature on the cancer cell. And there are several antibody-drug conjugates that are in development at various levels of promise in this space, particularly in EGFR-mutated non–small cell lung cancer, and I anticipate seeing some emerging data for that coming up in the near future as well. So really, lots to be excited in the space and lots for our committee to review to give guidance on so that these patients can really receive the top-level care wherever they are being treated in the country and throughout the world. Brittany Harvey: Yes, we'll await this new data to continue to provide optimal options for patients with stage IV non–small cell lung cancer with driver alterations. So, Dr. Reuss, I want to thank you so much for your work to rapidly and continuously update and review the evidence for this guideline and thank you for your time today. Dr. Joshua Reuss: Thank you so much. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available on the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Lyudmila Bazhenova is back on the podcast to discuss the latest update of the living guideline on therapy for stage IV NSCLC without driver alterations. She shares the studies the Expert Panel reviewed in the first- and second-line settings, including NIPPON, HARMONi-2, and DUBLIN-3. Although these studies do not impact the existing guideline recommendations, Dr. Bazhenova provides context and comments on ongoing trials that will influence the next iteration of the living guideline. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2025.1" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-01062 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2025.1." It's great to have you back on the show today, Dr Bazhenova. Dr. Lyudmila Bazhenova: It's my pleasure to be here. Brittany Harvey: And then before we discuss this guideline update, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Bazhenova, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into the content here, Dr. Bazhenova, this living clinical practice guideline for systemic therapy for patients with stage IV non–small cell lung cancer without driver alterations is updated on an ongoing continuous basis. So what prompted this latest update to the recommendations? Dr. Lyudmila Bazhenova: Living ASCO guidelines are designed to keep pace with rapidly evolving evidence that impacts treatment of our patients with lung cancer. As a committee, we are tasked with regular review of the published literature and determine if the new data warrants changes to existing recommendations. So in this recently published update, we evaluated new trials related to treatment of patients with metastatic lung cancer without driver alterations. Brittany Harvey: Excellent. Thank you for that explanation of the process. So, you just mentioned that the panel reviewed new trials for this update. So, which particular updated evidence did the panel review on first-line treatment options for patients with good performance status across histology and PD-L1 expression status, and how did this impact the recommendations? Dr. Lyudmila Bazhenova: For the first-line treatment option for patients without driver alterations, two studies met our criteria for review. One was the NIPPON trial from Japan, the second was the HARMONi trial. None of those two trials resulted in change in our guidelines, but I think they are giving us some additional information that would be useful for the way we treat patients with non–small cell lung cancer without driver alterations. For example, if we take those patients, we currently have several treatment options as a first line. One is monotherapy immunotherapy. You can give pembrolizumab as an example, and that was based on the KEYNOTE-024 and KEYNOTE-042 trials. Then we have a platinum doublet plus immunotherapy, and there are several trials that did that pathway. And then we have also an option of giving our patients dual IO immunotherapy combination, such as CheckMate 9LA and POSEIDON. At this point, we do not have any randomized trials comparing those three treatment modalities head-to-head. And the NIPPON trial was interesting to us because it was the first trial to compare CheckMate 9LA regimen, which is again, dual immunotherapy plus chemo, versus KEYNOTE-189 or KEYNOTE-407, which is a chemotherapy plus immunotherapy. And as a result of the study, while chemotherapy plus ipilimumab-nivolumab led to numerically higher overall survival, the difference was not statistically significant. And what is concerning in that trial is that we saw a higher number of treatment-related death occurring in nivolumab and ipilimumab arm compared to the pembrolizumab-chemotherapy arm. As a matter of fact, the trial was terminated early because of the increased risk of death. If you look at the treatment-related death in CheckMate 9LA, the 9LA study reported the treatment-related death to be 2%, and then in the NIPPON trial, the treatment-related death was 7%. Why is that happening? It's really difficult to say. The study was done in Japan. Maybe there is some pharmacogenomic differences between global population and Japan population. But certainly the higher rate of adverse events needs to be taken into account. Another interesting thing about this trial is that it did not show any differences in a subset analysis for patients with squamous histology as well as PD-L1 negative tumor. So while this does not change our current guidelines and CheckMate 9LA treatment still remains an appropriate treatment option, it kind of raises the possibility that this combination could be associated with a higher toxicity. And we do have a randomized US-based trial that is ongoing, and we are hoping that eventually we will be able to answer that question after the trial will be completed. The second trial we reviewed is HARMONi-2. So HARMONi-2 was a randomized, double-blind study which is conducted primarily in China, looking at bispecific PD-L1 and VEGF antibody called ivonescimab. And that took patients who were PD-L1 positive, as defined as more than 1% expression, and patients were randomized to pembrolizumab versus bispecific ivonescimab. And the study was positive. It showed improvement in median progression-free survival of 11 months versus almost 6 months in bispecific versus pembrolizumab. There were, however, higher grade 3 events in the ivonescimab arm. At this point, we are not changing our recommendations because this trial was done in an ex-US population, and we are awaiting a similar trial ongoing in the United States before we change recommendations and decide if ivonescimab needs to be included in our guidelines. Brittany Harvey: This context is very helpful when clinicians think through the data behind these options. And it's important that the panel reviews this evidence, even if it doesn't prompt a change to the recommendations. And we'll await results of those trials that you mentioned to further inform this guideline. So then beyond those studies for first line, what updated evidence did the panel review for second-line and subsequent treatment options for patients with good performance status, and how did this impact the recommendations? Dr. Lyudmila Bazhenova: So for second line, only one trial met the criteria, and that was DUBLIN-3. DUBLIN-3 is a phase 3 single-blind randomized trial comparing docetaxel versus docetaxel plus plinabulin. And the study enrolled patients with second or third line. They have to have had platinum-based chemotherapy and progressed. Plinabulin is an interesting compound. It's a small molecule tubulin binder that prevents polymerization of tubulin and appears to impact dendritic cell maturation and T-cell activation. This study enrolled 559 patients, randomly assigned them to two groups. And one important information about this study is that was a study that was envisioned before immunotherapy became a standard mainstream treatment for first-line therapy. And only 20% of patients had prior PD-1 exposure. So therefore, the results of that study need to be taken into context of this population no longer existing in the United States because we use PD-L1 inhibitors in the first line. And we saw that interesting in the plinabulin arm had lower rates of neutropenia but higher rates of serious adverse events. And at this point, we are not changing our guidelines for mainly two reasons. Number one, low number of patients that received prior treatment with first-line immune checkpoint inhibitors, as well as a modest overall survival benefit of this trial. Brittany Harvey: Understood. I appreciate you describing that study as well and why that evidence didn't prompt a change to those particular recommendations. So then, what should clinicians know as they implement this living guideline, and how does this new evidence impact clinicians and patients? Dr. Lyudmila Bazhenova: At this point, none of the studies that we reviewed resulted in a change in guidelines. We are still waiting for more global results from some of the studies that I highlighted. It shows that there's still a lot of questions we need to be answering in those patients. And I'm hoping that with future clinical trials, we will be able to definitively maybe recommend one treatment over another. But at this point, all the treatments that I mentioned before remain appropriate for patients with stage IV non–small cell lung cancer without driver alterations. Brittany Harvey: Definitely. And then you just mentioned that there's still a lot of outstanding questions in this field. You've mentioned a couple different studies where we're awaiting evidence. Beyond those that you already mentioned, what is the panel examining for future updates to this living guideline? Dr. Lyudmila Bazhenova: Right now, our next task is to come up with a full guidelines update. ASCO have certain rules for the guidelines committee members. And so we are gearing for a full guideline update, which hopefully will be ready by the end of 2025. Brittany Harvey: Excellent. We'll look forward to that full update of the living guideline, and we'll still await results of these ongoing trials to further inform this living guideline. So I want to thank you so much for your work to rapidly and continuously update this living guideline, and thank you for the time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: My pleasure. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Luis Raez and Michael Reff share the newest update to the medically integrated dispensing pharmacy standards from NCODA and ASCO. They review updates to domain one, on key patient-centered quality standards on health equity and social determinants of health, drug access, patient safety, education, and adherence to maximize treatment outcomes and domain two, on key operational quality standards on logistics, care coordination, and waste prevention. We also cover the impact of these updated standards for clinicians, oncology practices, and people receiving oral anti-cancer medications. Read the complete standards, "Medically Integrated Dispensing Pharmacy: ASCO-NCODA Standards." Transcript These standards, clinical tools, and resources are available on ASCO.org.  Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the JCO Oncology Practice. Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.  My name is Brittany Harvey, and today I'm interviewing Michael Reff from the Network of Collaborative Oncology Development and Advancement and Dr. Luis Raez from Memorial Cancer Institute and Florida Atlantic University, co-chairs on "Medically Integrated Dispensing Pharmacy: American Society of Clinical Oncology – Network of Collaborative Oncology Development and Advancement Association Standards Update." Thank you for being here, Michael and Dr. Raez. Dr. Luis Raez: Thanks for inviting us. Michael Reff: Thank you for having us. Brittany Harvey: Then, before we discuss these standards, I'd like to note that ASCO takes great care in the development of its standards and ensuring that the ASCO Conflict of Interest policy is followed for each guidance product. The disclosures of potential conflicts of interest for the expert panel, including Michael and Dr. Luis Raez who have joined us here today, are available online with the publication of the standards in JCO Oncology Practice, which is linked in the show notes. So then, to dive into the content here, Michael, I'd like to start with what prompted an update to these ASCO-NCODA standards and what is the scope of this update? Michael Reff: Thank you, Brittany. What led NCODA and ASCO to endeavor in this, and it started back in 2019 as the amount of oral anticancer medications became more and more prevalent in cancer treatment, we saw the need providing a blueprint for excellence in care for patients prescribed oral anticancer medications, specifically in the outpatient setting. And the update was driven by the rapid growth of these oral oncolytics starting back in the mid to late 2015 through 2019 or so, and then continued on into the 2020s where we are today. We saw the increase in the complexity of the management of these patients with these therapies basically outside the traditional clinical settings. And we wanted to make sure that with more cancer treatments that are taken at home than just at the clinic, like in the oral setting, new challenges had emerged around patient safety, access, adherence, and overall treatment success. The updates now address patient-centered and operational interventions designed to improve access, safety, quality, accountability, and outcomes of oral anticancer and other supportive care medications prescribed for the cancer patient. Dr. Luis Raez: As Mike said, these guidelines help improve patient care tremendously, but also help us a lot as an oncologist, you know, community oncologists that- now that we have opportunity to dispense these oral oncolytics, we need help to create our medical integrated pharmacies, and NCODA is providing here a way that, how to do this safely, efficaciously, good quality, you know? So that's why I think we always do everything for the patients, but also this helps a lot to the doctors. And there are a lot of what we call specialty pharmacies or medical integrated pharmacies now nationwide. Michael Reff: I'll build on what Dr. Raez had mentioned. This is the impetus. If you looked at the innovation that was coming from the pharmaceutical companies, many of it coming in the oral form for anticancer medications, and based on that, taking a look at the infrastructure that is in place in these practices, whether it's in the community or the IDN or health system settings, this amount of innovation that was coming needed to be addressed by taking a look at the medically integrated oncology team. And these standards address not just the pharmacy component, but also the whole continuum of care, starting with a medical oncologist or the hematologist, with the pharmacists, nurses, the pharmacy technicians, others that are involved in the care of the patient. And there were no standards involved. And when we approached ASCO back in 2018 to eventually publish the first version of these standards, the need was identified, and we worked collaboratively with ASCO to create the first set and then the revisions as we talked about. One thing to note regarding the revision plus the original standards, we had a cross-section of the care team on the committee, and we did that very purposefully. So, the ASCO-NCODA team curated a committee to help develop these original standards and the revision of these standards with medical oncologists both from community and health systems, pharmacists from both community and health systems, and also nurses. And we also included a patient that currently has and currently receives oral anticancer medication. And so NCODA and ASCO are very proud of the committee that we put together because of the experts in their field, but also extended the invitation to a current patient. And we embedded everybody's expertise in the curation of these standards. Brittany Harvey: Absolutely. I appreciate that background and context and how it's critical to improve patient care. And these standards really help oncologists, and we're looking across the continuum of care to provide optimal care for our patients. So then next, Dr. Raez, I'd like to review the key points of the revised standards for our listeners. So for Domain 1, what are the key patient-centered quality standards on health equity and social determinants of health, drug access, patient safety, education, and adherence to maximize treatment outcomes? Dr. Luis Raez: Yeah, this was a great effort, you know, at the multidisciplinary team. And as you can read in the standard, there were more than 240 publications reviewed; more than 55 of them are quoted here. And the standards are in two groups, as you said. With the group one, I'll briefly mention some of them. For example, SDOH, social determinants of health, is very important because as doctors, we prescribe, and sometimes patients don't get the medication, you know? And we prescribe assuming that 100% of the patients will get the medication. But something simple like the patient doesn't have insurance, the patient is underinsured. I have a patient that we didn't have an address to send the medication because he's homeless. Something that as a doctor you say, "Oh, oh my God, this is outside my realm," but it's not outside reality. So that's why, even if we don't think that this is part of our expertise dealing with social determinants of health, the fact that the patients have food insecurity, they don't have transportation, they don't have insurance, they don't have a caregiver, impact tremendously in the outcomes of the therapy. So that's why, basically, in this standard, we want to call attention that SDOH, social determinants of health, needs to be identified. There are in the literature countless examples of why this is important. For example, in the guidelines, we quote two or three examples of prostate cancer studies that, for example, we quote a study of 27,000 people with prostate cancer that were taking oral oncolytics, and how come the fact that the elderly, seniors, the fact that they have high prescription costs, and how all of this affected the adherence to the medication. And that's why it's important to identify the SDOH. And in other sections of the guidelines, we said how to address them, no? Another important thing in this domain is the cultural, you know, we need to be culturally sensitive and to take care of all of these social factors. For example, here in South Florida, we deal with the Haitian culture, Filipino culture, Latin culture, and American culture, and it's a blend, but it's not easy to go from one to the other. Another one is the fact that we have to include new technologies. A lot of patients, for example, we use EMR, EMR Epic, and now Epic has everything in the phone. The fact that we can have now the patient can see her prescription medication over the phone, the fact that they can use the phone to request from you a refill, and from your phone, you send the refill to the pharmacy, and you notify from your phone to the patient that the refill is sent, and the patient can check in his phone that the refill is ready. These things are amazing because that's why it's important that we incorporate these technologies to the patient care, and in this specific case, of dispensation of oral therapies, no? Another crucial point is education. You cannot be sending a patient a package of 300 pills without education. So that's why in our guidelines, mainly pharmacy, clinical pharmacies, or in some centers like mine, we have advanced practice providers, it's mandatory in our centers to have like a one hour of education before you send the prescription. So the patient is aware about side effects and contraindications, all of these things. They provide them also materials and also consent. You know, in the old times, you don't give chemo without a consent. Now, a lot of people say, "Oh, it's only a pill." There is a lot of benefits or side effects that can come from the pill, so you need to consent everybody, you know? So, another aspect is adherence. I already told about that, but we need to provide patients with a baseline assessment, no? So, you cannot send again the prescription and hope, "Oh, I'll figure it out what happened next month when the patient comes back." I tell you, the patient is homeless, where are you going to send it? If the patient is telling you, "I don't have insurance," what good is it for you to send a prescription? The patient will not get it. So that's why you need to do a baseline assessment of adherence. You need to do a calendar. You need to do electronic support, I mentioned already with the EMR and the phones. For example, my MIP, my specialty pharmacist, sends me a message in the EMR, "Dr. Raez, the insurance is not covering, the patient has a high copayment, we are going to delay the dispensation of the medication." So there needs to be a communication. Or sometimes there is a confusion with the insurance, and I cannot wait for the poor patient to call three, four weeks later, "Oh, I didn't get the medication," to know what happened, no? My MIP is very good. They send the clinical pharmacist a message, "Hey, you know, the insurance doesn't believe that the pill is adequate, or you need to provide more documentation. You need to prove the mutation, the genetic aberration." So if you provide us that, the insurance may approve. So that communication with the doctor is very important to improve adherence. And one important thing that we have in this one that we didn't have in the anterior is the tracking of outside medications. A lot of times you say, "Okay, the insurance allowed us to provide the medication it's 100% responsible." But then the insurance says, "Oh, no, no, don't worry. CVS will provide the medication." So it says, "Well, it's you know, it's not my responsibility. CVS will provide the medication, they have to take care." But we know that outside our specialty pharmacies or MIPs, the care is not very good. So that's why we are taking our ownership that, "Okay, the insurance said the patient will get the medication from some outside pharmacy." But our clinical pharmacists track that. What happened? Did the patient get it? The patient didn't get it. The copayment is still high. So even if you get the medication from somewhere else, if the copayment is high, we, our clinical pharmacists, help the patient to navigate and get the foundation or the copayment or finally the maker, the industry partner, provides the drug for free, but somebody needs to do the paperwork. And that's why this is very important. We cannot abort our responsibility because, "Oh, the insurance said somebody else will give it." I work for the public healthcare system, so my patients, some of them don't have insurance, they are underinsured. So we see these problems every day. And finally, the standards talk about the importance of safety, documentation, verification, monitoring, refills, you know, you need to keep track of refills. We already mentioned how important is the technology to facilitate the refills, and the quality. Brittany Harvey: Yes, thank you for touching on those highlights for Domain 1. It's important that all patients have access to care and these oral anticancer medications, and not only just access to care, but safe and effective care. It's really important, as you mentioned, Dr. Raez, to meet patients where they're at and incorporate technology. And I also want to note the coordination with external pharmacies that you mentioned in tracking outside medications as well. It's not only important for multidisciplinary care within the oncology practice itself, but also external to the oncology practice. That's why we put together this multidisciplinary panel to develop these standards. So then, expanding on that, Dr. Raez, for Domain 2, what are the key operational quality standards? Those on logistics, care coordination, and waste prevention. Dr. Luis Raez: Yeah, we have a lot of standards here, but maybe we can summarize in five or six points, no? For example, financial toxicity in cost and waste are very important because the patients, yeah, you put them on therapy, but as you can understand, if there is disease progression, the patient don't need the medications. And sometimes you get refills even if the patient has disease progression. If you do a dose reduction, the same problem. Or you discontinue medication and the patient keeps getting the drugs. So, you're talking about drugs that are between 20 and 30 thousand dollars per month. This is a lot of money. There are studies that we're quoting in the standards that the waste could be from 1 to 3 or 4 thousand per patient, no? Another aspect is dispensing. When you dispense the medication, this is not as easy as, "I'll ship to your house a bag of medications." You know, there needs to be a diagram, a decision tree. You need to train the staff to know what we're doing. There needs to be an auditing of the process. They need to be even packaging and shipping, you know? For example, I'm in Florida today and outside in summer it's going to be 95 degrees. So, everybody leaves the package outside your house, and sometimes you go the whole day until when you come at 6:00 p.m. There are medications that cannot be left outside there, you know? I don't know, it sounds like a joke, but I have a patient that the medication used to be stolen because people thought that that was something important, you know? And of course, it's important because it's a $20,000 medication. So, the poor patient, because he lives in an area that is not safe, has to come and pick up in person. All of these things sound very trivial, but that's real life that affects adherence. Another important thing is shortage. This is something that we just suffered two or three years ago, and we have to think about what happens in the next shortage. What happens if there's going to be a shortage? What do we do or how are we going to do that? Now we know it's something that is happening probably very soon again, and something that we have to consider. Another standard is the care coordination. You need to have probably, if it's possible, a coordinator. I know that for small practices it's very hard, but for big cancer centers, you should have a coordinator of this. I already mentioned before, the communication between the physicians and the doctors to coordinate the care, no? You need to write the prescription again, you need to provide more information, or to be notified, "Hey, you know, the patient is throwing up in the first week, you need to see the patient, please," no? So, this type of communication needs to exist so we can serve the patient better. It's also important, you know, we're improving quality and we're improving care. It's important to try to collect patient-reported outcomes. This is something that now we have the opportunity, if we do things well, to do it and show that we're providing a better care. The other thing is that we already mentioned SDOH in the other standard. In this standard, we mention mainly SDOH to partner. For example, we collect in my center SDOH, and I always get frustrated when the patient doesn't have transportation. But I didn't know that there are local institutions that provide free Uber rides, free Lyft rides. So that's why it's important to partner with these institutions. I have a local grocery chain that provides free food for the patients, and I didn't know that. It's important to be aware what the patient needs and what resources do you have to fulfill the SDOH. That's the part that we mention in here. So that's why, in summary, those are the six probably most important points here. I'll ask Mike for some comments. Michael Reff: Thank you, Dr. Raez. Brittany, to answer your question, and as was pointed out on logistics, care coordination, and prevention of waste, certainly that is an aspect that has changed in the revision that we're here to talk about. There's really two components to waste, and it's cost avoidance and then waste prevention. And as Dr. Raez mentioned several times, the importance of the medically integrated team and having the ability for that practice to fill that prescription internally and have robust documentation. Cost avoidance is a critical component that the medically integrated pharmacy, or the MIP, can help the total cost of care. And that is by preventing errant fills or waste that can occur by intervening in the care of the cancer patient, as we do every day. But when the practice has access to the medication and can fill that prescription in-house in the medically integrated pharmacy, that team, that care coordination that takes place, can prevent those errant fills or additional fills when there's dose reductions, there's holidays, there's things that happen in real time. And it's impossible for a mail-order pharmacy that's in another state that has lead times, when a prescription needs to be mailed 7 days or 10 days before the patient will run out of the medication, it's impossible for them to logistically coordinate that care like we can internally within the medically integrated pharmacy. So, we prevent waste and overall cost of care by cost avoidance and having that coordination or that continuity of care that we talk about. And we prevent waste from the mail-order pharmacies by taking that prescription internally and filling it, but also doing it in a way that's more sustainable and cost-effective for all stakeholders in the oncology ecosystem. Brittany Harvey: Absolutely. Thank you both for reviewing those key standards for Domain 2 and touching on the importance of distribution logistics and all the things that a medically integrated pharmacy needs to think through in getting oral anticancer agents to patients. Following that, Michael, we've touched on this a little bit earlier, but how will these updated standards impact clinicians and oncology practices? Michael Reff: Yes, and as Dr. Raez and I have discussed throughout this podcast, these additional standards are there to help support that continuity of care by educating the clinicians that are in the oral anticancer medication space to elevate their provision for these oral therapies. What I mean by that is the practice has to perform at a certain level in order for them to, as I call it, deserve the right to fill that prescription by having the processes and procedures in place. And these standards, these updated or revised standards, are the blueprint for better patient care and to help the practices execute on that journey of continuous improvement. Dr. Luis Raez: Yeah, I only want to add, we have practical examples in the guidelines. We quote a couple of studies that have been successful. And this year, for example, I am a lung cancer doctor, we are presenting in World Lung our standards of adherence to oral oncolytics for EGFR therapy, following the NCODA-ASCO standards. We're around 95% of adherence. We are a healthcare system that is public. We have people with no insurance and a lot of social determinants of health. We are trying to show that it's feasible, even in the most difficult circumstance, when you follow the standards, to be successful. Brittany Harvey: Definitely, these standards can help clinicians and oncology practices succeed in providing these medications. So then beyond that, and to wrap us up, Michael, what do these revised standards mean for patients who are receiving oral anticancer medications? Michael Reff: Yes, great point and question, Brittany, because we have covered the benefits to the clinicians and the practices themselves. But how is this going to support better patient care? And it does it in a whole host of ways. I'll cover just a few of them. What I'm about to share with you relates back to what we call at NCODA the "core claims." Like, what's the core claims of having a medically integrated pharmacy within the practice? And there are seven different core claims that we feel practices that are focused on the continuity of care can deliver better outcomes that are embedded in these standards. And it's talking about abandonment, adherence, access and affordability, speed to therapy or time to fill, as we call it, education, patient satisfaction, and cost avoidance that we covered earlier. So those are the core claims that a practice that follows these revised standards can help elevate. So, faster and more affordable access to the oral cancer medications; individualized support to address barriers like transportation, finance, language, or health literacy, and so on; clear, patient-friendly education; something that is near and dear to all clinicians' hearts, and of course, the patient that was on our panel or on our committee, to empower them to manage side effects and recognize when to seek help; and a stronger partnership with a care team, with regular follow-ups focused on their experience, challenges, and successes; and then, greater overall safety through proactive monitoring for medication errors or complications. So all of these aspects, or tenets, as I'll call them, are baked into these quality standards that are totally aligned with NCODA's core claims document that, again, talks about abandonment, adherence, access and affordability, speed to therapy, education, satisfaction for the patients, and also cost avoidance. Dr. Luis Raez: I only want to add and invite the community to adhere to these standards, to practice the standards. You will be providing the best patient care that we can nowadays. Brittany Harvey: Definitely. I think these standards are very important. And Michael, I thank you for touching on those key claims from NCODA. I think those, along with these updated standards, will improve outcomes for patients everywhere. So I want to thank you both so much for your work to update these standards and all the time you put into it. And thank you for your time today too, Michael and Dr. Raez. Michael Reff: I'd like to thank not only the committee, my esteemed committee that helped support the standards and the revision. Many of the original healthcare providers and patient that were on the first go of the standards were part of the second standards. We revised it, of course, and we got additional support from the new committee. And certainly ASCO and their partnership and collaboration with NCODA has been tremendous. And we look forward to the oncology community at large adopting these standards, again, to work together, we do become stronger, and it will improve cancer care for patients receiving oral anticancer medications. So thank you, Brittany. Dr. Luis Raez: I only want to say the same thing. Actually, there is probably more people in NCODA that is not in the publication that has helped. Same in ASCO. Also, we want to give thanks to Dr. Stephen Grubbs, our leader in quality. He's retiring. We're going to miss him, but he has been a key collaborator with Mike organizing these standards for the last five or six years. So, looking forward to these standards in practice. Brittany Harvey: Absolutely. A big thank you to the entire panel and everyone who contributed to this, and NCODA as well. And then finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the complete standards, go to www.asco.org/standards. I also encourage you to check out the companion episode on these standards on the PQI podcast by NCODA, which you can find on Apple Podcasts and Spotify. You can also find many of our standards 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've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Kimberly Perez and Dr. Jaydira Del Rivero discuss the new guideline from ASCO on symptom management for well-differentiated GEP-NETs. They share the latest recommendations on managing symptoms related to hormone excess, including carcinoid syndrome and carcinoid heart disease, managing symptoms of functioning pancreatic neuroendocrine tumors, and also palliative interventions. Dr. Perez and Del Rivero share how to use this guideline in concert with the systemic therapy for tumor control in metastatic well-differentiated GEP-NETs guideline, and hope for the future for the treatment of gastroenteropancreatic neuroendocrine tumors. Read the full guideline, "Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline." Transcript This guideline, clinical tools, and resources are available on ASCO.org. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in JCO Oncology Practice.        Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Kim Perez from Dana-Farber Cancer Institute and Dr. Jaydira Del Rivero from the Center for Cancer Research at the National Cancer Institute, co-chairs on "Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline." Thank you for being here today, Dr. Del Rivero and Dr. Perez. Dr. Kim Perez: Thank you. Dr. Jaydira Del Rivero: Thank you so much for the invitation. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Perez and Dr. Del Rivero, who have joined us here today, are available online with the publication of the guideline in JCO Oncology Practice, which is linked in the show notes. So then to jump into the content here, first Dr. Del Rivero, could you provide an overview of the scope and purpose of this guideline? Dr. Jaydira Del Rivero: Yeah. Thank you so much. Well, first, we really wanted to thank ASCO for allowing us to develop these guidelines for the management of gastroenteropancreatic neuroendocrine tumors. I do want to mention that there is also another set of guidelines that I was very fortunate also to co-chair with Dr. Perez on the systemic management of gastroenteropancreatic neuroendocrine tumors. But when discussing these guidelines as well as with the different panelists, experts in this type of disease, we also realized that the management of these tumors are quite complex, not only from the management of the disease progression, but at the same time, management of the symptoms related to the hormone excess. And because of that, we like to thank ASCO for allowing us to then not only have a discussion on the systemic management of these tumors, but at the same time develop recommendations for the symptoms related to the different hormones that these neuroendocrine tumors may produce. These guidelines are for the management of grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors. These guidelines include the management of the different aspects and the symptoms related to hormone excess, such as carcinoid syndrome, carcinoid heart disease, how to manage carcinoid crisis, as well as the different symptoms and how to manage the functional pancreatic neuroendocrine tumors and as well as provide recommendations in the different treatments for these tumor types, not only from the systemic management but also from the surgical management as well as for liver-directed therapy options and the different aspects in terms of the palliative care of these patients to improve not only the symptoms related to the hormone excess caused by these tumors, but as well as to improve the quality of life. Brittany Harvey: Absolutely. And I appreciate that overview. And yes, we'll link the guideline on the Systemic Therapy for Tumor Control for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors in the show notes for our listeners so that they can refer to that companion guideline as well. So then you just described the several different categories of recommendations that this guideline covers on symptom management. So, Dr. Perez, I'd like to start reviewing some of those key recommendations of that guideline. So, starting with what are the key recommendations for carcinoid syndrome and carcinoid heart disease? Dr. Kim Perez: Thank you Brittany. Yeah, I also want to thank ASCO for inviting us to do this podcast today. Just to start, I think these guidelines will really add to what's available in the literature to provide a kind of a quick look for the community provider to manage carcinoid-related symptoms. I think the highlights that I would point out are we've all been using somatostatin analogs for the last few decades to manage symptoms, but with the newer treatments that are now available, we tried to highlight what does the literature support in regards to PRRT, what does the literature support in regards to using systemic therapy for disease management, but also the benefits that you will get from a symptom management perspective using other modalities. I think the highlight really is it's a multidisciplinary approach. We are now considering surgery and embolization or interventional radiology as a critical piece. And I think the third that I'd highlight is the fact that sometimes we get too focused on carcinoid syndrome and the symptoms will actually, may result from other things. And the highlight in the algorithms that we've provided is what other things cause carcinoid-related diarrhea. And let's not forget about that because we will find ourselves treating and patients getting very frustrated with persistence of symptoms when in actuality, we should be treating something else that is causing a very similar symptom. For carcinoid heart disease, I think there are more and more guidelines that are now available to provide guidance there, but I think the major advances are that we should be utilizing heart assessment with echocardiogram with lab values such as BMP. But also critical to this is consulting with our cardiology colleagues and making sure that we're identifying heart related issues that are resulting from hormone excess sooner than later because interventions on the earlier side can really make a significant impact on quality of life and associated comorbidities and mortality. Brittany Harvey: Thank you for reviewing those key points for both carcinoid syndrome and carcinoid heart disease symptom management. So then the next set of recommendations. Dr. Del Rivero, what are the key highlights for symptom management of functioning pancreatic neuroendocrine tumors? Dr. Jaydira Del Rivero: Yes, it's very important to recognize the symptoms related to hormone excess due to pancreas neuroendocrine tumors. Up to 10% of pancreas neuroendocrine tumors may produce different hormones. Among those hormones can be insulin, gastrin, glucagon, somatostatin. So it's important to know and understand that based on what a neuroendocrine tumor is, they may produce different types of hormones. The importance of these guidelines is to also recognize some of these symptoms and how to address that, because it's not necessarily in these tumor types besides the management of metastatic disease, and know the different options that we recommend for metastatic disease from the systemic therapy, such as chemotherapy or targeted therapies or PRRT. It's important to recognize the symptoms because based on the symptoms we may recommend a different approach. That's something that is important to acknowledge and recognize. Moreover, in certain functional pancreas neuroendocrine tumors, as Dr. Perez mentioned, is a multidisciplinary approach. And it's important to also discuss these different cases with your endocrinologist. You may need to have an experienced endocrinologist to manage, for example, the excess of insulin. And also discuss your cases with a surgeon and interventional radiologist because some of these approaches can certainly improve the symptoms related to hormone excess. I understand that sometimes medical oncologists in the communities may not have access to the multidisciplinary approach or have the different teams that can manage these tumors, and that's the reason why with these guidelines we wanted to establish the understanding of different symptoms associated with the hormone excess to these neuroendocrine tumors as well as how to manage this. For example, in the case of insulinoma, I think for the medical oncologist it is important to know that the everolimus is an option to be used for these tumors, not only to manage tumor progressions related to this tumor type at the same time, because everolimus as a side effect causes hyperglycemia, that can also improve some of the symptoms related to the excess of insulin besides the somatostatin agonist. I think these recommendations will allow the medical oncologist to recognize the symptoms and based on what the symptoms cause, then you can have a different approach that could be added to the systemic therapies options as well. Brittany Harvey: Yes, beyond systemic therapy, it's important to be recognizing symptoms to provide an individualized approach for every single patient. So then, following that overview of symptom management for functioning pancreatic neuroendocrine tumors, Dr. Perez, what is recommended regarding palliative interventions for patients with gastroenteropancreatic neuroendocrine tumors? Dr. Kim Perez: Yeah, great question. So I think what's unique to neuroendocrine tumors is that the palliative approach really mirrors what we would be doing for symptom management. Some of these patients are living a very long time with carcinoid related symptoms. And so the approach that we take for the carcinoid symptom control is going to mirror the palliative piece of it. I think for those who develop a burden of disease related symptoms, I think it mirrors what we do across the board for all cancer-related complications. And so I think what we attempted to highlight here and included one of our colleagues who focuses specifically on the field of palliative care and neuroendocrine tumors, was to never really lose sight of what we've been doing to care for symptom management throughout the patient's journey and to always rereview the etiology of the symptoms, ensure that we don't focus solely on carcinoid-related issues, but also the symptom management that we would apply to all patients with cancer-related burden symptoms. Brittany Harvey: Definitely. I think that's a helpful approach to consider when thinking about how to manage these palliative interventions as well. So then Dr. Del Rivero, what should clinicians know as they implement these symptom management recommendations? Dr. Jaydira Del Rivero: Yes, thank you so much for that question. As we have discussed in the last 10 or 15 minutes, we have discussed the different approaches on the management of gastroenteropancreatic neuroendocrine tumors. Clinicians, I think it's important to know that neuroendocrine tumors is a quite complex disease because we're not only addressing the management of tumor growth, but we're also addressing the management of the symptoms related to hormone excess and the complexity associated with that. When medical oncologists or clinicians implement these recommendations it's to understand what symptoms these tumors may cause related to the hormone excess but at the same time, how do we approach those symptoms? As Dr. Perez said that I think is very important is to recognize the different types of diarrhea. It doesn't mean that if the patient has worsening diarrhea, it doesn't mean that this is related to disease progression. So it's important to recognize so that way you can address that, because the type of diarrheas can be related because of the lanreotide or somatostatin agonist, it could be because of the prior surgery. I think it's important to recognize those in order to address the symptom. And the same with the gastroenteropancreatic neuroendocrine tumors. It's important to know what hormones they produce because there are different measurements that may be added to the systemic management of these tumors. I think that there are two aspects here, and that's the reason why these guidelines were implemented in the sense that not only we're going to manage disease progression of these tumors, or how do we manage the metastatic disease of these tumors, but at the same time, how do we manage the symptoms related to the hormone excess and the different complications. Moreover, I think, as we discussed earlier, we need to manage these tumors in a multidisciplinary approach. And something very important is not like one size fits all, because the treatment recommendations, it will depend on different characteristics in terms of the tumor presentations. And hormone excess is one of the important aspects to recognize so that way we can implement these recommendations that will definitely help the quality of life of these patients. Brittany Harvey: Absolutely. And using these guidelines in concert with the systemic therapy guidelines is key. And then beyond this impact for clinicians that Dr. Del Rivero has just outlined, Dr. Perez, what does this new guideline mean for patients with gastroenteropancreatic neuroendocrine tumors? Dr. Kim Perez: Yeah, I think that's an important highlight of this guideline. It really gives patients a voice. I think it recognizes the fact that these symptoms can go unmanaged or mismanaged or just missed, and patients commonly will come in feeling very frustrated and feeling very ill. And I think it will provide them a means to open up a conversation with their providers and say, "Hey, this is what I'm experiencing. Let's talk about what's available. How does this apply to me?" And I think that can be very empowering. I think it's really hard nowadays with so many sources and resources online and patients are really left wondering what are the bullet points that they should be bringing to their clinician appointments? And I think that these guidelines provide them a good framework for those discussions. Brittany Harvey: Yes, bringing these discussion points for patients is very important to be able to have those resources. And we have some patient resources and information available on the website for this guideline and we can link that in the show notes for listeners. So then you've both touched on the importance of this guideline for improving quality of life and we continue to see advancements in this field. So Dr. Del Rivera, what are the outstanding questions regarding symptom management and tumor control for gastroenteropancreatic neuroendocrine tumors? Dr. Jaydira Del Rivero: I have to say whenever somebody asks me that question, the word that I will say is I feel hopeful, because more than 10 years ago we didn't have that many options for gastroenteropancreatic neuroendocrine tumors. And it has been in the last decade or so that there has been more developments in the management of these tumors as well as the understanding of the symptoms related to these tumors. But that said, yes, we do need more therapies for gastroenteropancreatic neuroendocrine tumors. Of the treatment options that we have, we all know in the field that even though we have disease control by using the different options for the systemic management of gastroenteropancreatic neuroendocrine tumors, we need options where we can achieve an objective response, especially for these tumor types. But there is a significant volume of disease and we see a lot of these patients with gastroenteropancreatic neuroendocrine tumors. And now where the field is going is to make some of these therapies more effective, to develop more therapies as well. For example, immunotherapies, a different type of immunotherapy understand the tumor immune microenvironment of these tumors in order to develop therapies as well. From the antibody drug conjugates, I think that's a new way to also address or treat these tumor types, understanding about the different markers found on these tumors that way they can be addressed in different ways. Now with the development of new therapies, I think that's something that can help us as well not only have disease control and as well as having an objective response, but having a better objective response can certainly also help with the symptoms related to hormone excess too. In terms of other therapies, I think some of the issues that we encounter are like the refractory carcinoid diarrhea and how do we manage this. We do have therapies that can help us control the diarrhea in the refractory settings, such as telotristat. Telotristat is one of the newer medications that can help us control the refractory diarrhea. But that said, despite this, that we still encounter situations where it's sometimes difficult to control. I think in those situations it will be good to understand more about the biology of these tumors as well and how we manage. If there is a different time or how do we implement these options. I think there is so much to learn. But that said, I feel we're in hopeful times. We're understanding more about these tumors so that way we can help us develop better therapies not only to have control of the tumor growth as well having control of the symptoms. And it's the same with the pancreas neuroendocrine tumors in the metastatic setting. Sometimes it may be difficult to control this hormone excess. But understanding these and having therapies that can achieve more of an objective response, I think that will definitely help us more and manage these patients. But one aspect I want to mention, and Dr. Perez also mentioned as well, the fact that we have these guidelines that help us understand about the different symptoms related to hormone excess and how to address it, I think is very important because having symptoms related to hormone excess can be detrimental to the quality of life on patients with neuroendocrine tumors that may necessarily be related to disease progression and having this information is so important. And I'm hopeful for the different therapies. There's different clinical trials ongoing for neuroendocrine tumors and especially in the field of PRRT. And a lot of more information will come with the different alpha-PRRT and combination therapy. So more information to come in the next couple of years. So this is, in my opinion, hopeful times for this field. Brittany Harvey: It's great to hear that you're hopeful for all the developments in this field and we'll look forward to the development and discovery of new therapies and further research and then, hopefully incorporate those updates into guidelines in the future. So I want to thank you both so much for your work to develop these guidelines and thank you for your time today. Dr. Del Rivero and Dr. Perez. Dr. Jaydira Del Rivero: Thank you so much for having us. Dr. Kim Perez: Thank you. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. 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