Podcasts about jco

california children italy north america journal survivors assistant professor older similar pediatrics cancer survivors genoa asco childhood cancer health outcomes clinical oncology bhandari medical oncologist jco

Play Episode Listen Later Nov 20, 2025 21:22

Guest Dr. Rusha Bhandari and host Dr. Davide Soldato discuss JCO article "Health Outcomes Beyond Age 50 Years in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study, " with a particular focus on mortality data, development of secondary malignancies and the importance of education for both patients and healthcare providers regarding long-term follow-up and care. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Davide Soldato: Hello, and welcome to JCO After Hours, the podcast where we sit down with authors from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, Medical Oncologist at Ospedale Policlinico San Martino in Genoa, Italy. Today, we are joined by JCO author, Dr. Rusha Bhandari, a Pediatric Hematologist-Oncologist and Assistant Professor in the Department of Pediatrics and Population Science at City of Hope, California. Today, we will be discussing the article titled "Health Outcomes Beyond Age 50 Years in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." So, thank you for speaking with us, Dr. Bhandari. Dr. Rusha Bhandari: Thanks so much for having me. Dr. Davide Soldato: So, I just want to go straight ahead in the paper and start from the title. So, we heard that you included in this study childhood survivors of pediatric cancer that were aged 50 years or higher. So, this is a very critical life stage when we know that there are a lot of aging-related comorbidities that can happen, also in the general population but potentially specifically in childhood cancer survivors. So, first of all, I wanted to ask you, why this specific study in this very specific population? Because I think that we had already some data in younger survivors, but now we are focusing specifically on patients aged 50 or more. Dr. Rusha Bhandari: Absolutely. So, to answer that question, I'll take a little bit of a step back in terms of where we are now and where we came from in terms of treatment for childhood cancers. So, thankfully, we now have great curative therapies and survival rates for many childhood cancers, including the most common ones. But this was not necessarily the case 50 or more years ago. So, we essentially are now seeing the first generation of older survivors who are 30, 40, or more years from completion of their cancer treatment. As you pointed out, we know from younger survivors that they have a markedly higher risk of malignancies and health conditions than the general population. You don't typically expect to see things like heart disease or diabetes, for example, in a young adult. But the question that remained was what the health status and risk of these conditions are in survivors who are entering this critical age, as you mentioned, 50 or older, when you do start to see these aging-related changes in the general population. And the question is whether we're still observing increased risks related to cancer treatment that was delivered 30 or more years ago in these survivors who are now entering ages 50 and beyond. Dr. Davide Soldato: Thanks so much. You used the data from a study that is called the Childhood Cancer Survivor Study. So, just a little bit of explanation for our listeners. How is the study conducted? What type of data are you collecting? And specifically for the interest of the study that was reported in this manuscript, which outcomes were really important for you and were so evaluated in the manuscript? Dr. Rusha Bhandari: Yes. So, the Childhood Cancer Survivor Study is a really excellent resource that combines information from children who were treated across North America at various different centers and sites. So it gives us a really good understanding of how different survivors are doing as they do progress through their survivorship journey. The Childhood Cancer Survivor Study includes a baseline questionnaire when participants are first eligible or first enter the study, and then includes a series of follow-up questionnaires to really understand how they're doing, like I mentioned, as they progress throughout their survivorship journey. And so for this study, we really wanted to take a global look at how these patients were doing as they entered that older age range. And so we wanted to look at outcomes ranging from mortality through the health conditions that we've seen from other survivorship studies, including subsequent malignant neoplasms, other health conditions, I mentioned earlier heart disease and other comorbidities we know survivors can be at increased risk for, and also things like frailty, which we know is, you know, the most widely recognized phenotype of aging. And we see that earlier on in our younger survivors. We want to see how this translated to these older survivors and then also other health outcomes like their health status. What is their self-report of their physical health, their mental health? Things like that. So we wanted a very comprehensive understanding of their health. Dr. Davide Soldato: This is a very comprehensive study. Right now it includes more than 30,000 patients that have been treated for childhood cancer, but specifically looking at the question of survivors aged 50 years or higher, you included more than 7,000 patients inside of this study. So, looking at the first outcome that you mentioned, which I think it's also one of the most important, you look specifically at mortality, and in this specific population, you saw a striking three-fold increase in mortality when comparing these survivors with the general population. I just wanted to dive in this result and ask you: What do you see as the main driver for this excess mortality in this population of survivors? And as you were mentioning, the study also collects information about the treatment received. So, was there any association with a specific kind of treatment that was received for curing these childhood cancers? Dr. Rusha Bhandari: I agree. I would say it's striking to see that mortality risk among the survivors relative to the general population. And we do know, again from prior studies, that survivors of childhood cancer do have an increased risk of mortality compared to the general population, but I think looking at those curves of the cumulative mortality risk was really quite striking as they diverge, and that's, you know, just so long past their initial diagnosis and treatment. We know that subsequent malignant neoplasms or secondary cancers are a really an important contributor to mortality among survivors. And I think it was important to note that even in these older survivors, it's still such an important contributor to mortality, and I think this really highlights the need for us to better understand what is driving specific secondary cancers and what are the differences in the biology and treatment approaches for some of these cancers? And how might that then be contributing to the mortality risk? Dr. Davide Soldato: Related to the treatment mortalities - because I think that one of the main forces of the study, as it is conducted, is that it contains a lot of information regarding radiotherapy, allogeneic transplant, surgery, type of chemotherapy received by these survivors - so, are we able right now with the data that we have to pinpoint which of these treatments can potentially lead to such increased risk of mortality? Dr. Rusha Bhandari: So, we weren't able to look at the comprehensive treatment exposures and mortality risk for this paper. So that might be one of the questions I would put on the side. We were able to look at that in relation to subsequent malignant neoplasms and health conditions though, as you mentioned. Dr. Davide Soldato: Another thing that I think is very important is that you were able to look at specific causes for mortality. So for example, you mentioned the increased rate of neoplasm in this population and specifically, more or less 7.6% of the patients that were included in the study developed another neoplasm after the ones they were cured for in the childhood period. So, you saw a wide range of cancer, for example, bone and soft tissue sarcomas, breast cancer, genitourinary cancer. And as you were mentioning, there were some associations for treatment modalities that were associated with a higher risk of developing this type of cancer. Can you expand a little bit on this? Dr. Rusha Bhandari: Absolutely. And so the key part here was that we really looked at any of these outcomes that occurred beyond age 50. What we found was there is still an increased risk of secondary cancers beyond that initial childhood cancer diagnosis, but when we really looked at that data, it was specifically among survivors who had a history of receiving radiation. And we did not necessarily see an association between different chemotherapy exposures and secondary cancers. And I think this speaks to what we're now learning in terms of the very long-term effects of radiation and how that impacts ongoing health risk even in patients who are 30 or more years out from their treatment. And I think it really highlights the importance of these- the efforts that have been made in the more recent decades to really try and reduce or eliminate radiation where possible, you know, as we've come to understand more about these long-term effects from it. Dr. Davide Soldato: A clear association with radiation therapy but no association when we look at specific types of chemotherapy that were used for curing this childhood cancer. Another thing that I think it's very interesting and you briefly mentioned before is that potentially when we look at these secondary malignant neoplasm that develop in this situation, we might also see some outcomes that are not comparable to the one of the general population, meaning that we managed to cure less this type of cancer when they develop in these childhood survivors. So, I just wanted to understand if you could provide us with a little bit of perspective also from a clinical standpoint being a pediatric hematologist-oncologist as to why this might be happening and how can we potentially increase the cure rate also in this population of childhood cancer survivors? Dr. Rusha Bhandari: Absolutely. While that was not the focus of this study, it was something that we were certainly interested in is understanding how even once a childhood cancer survivor, for example, develops a health condition or a secondary cancer further into survivorship, how does that outcome then differ from someone in the general population? And there's a lot of interest in ongoing studies actually evaluating that and understanding what are the differences from the initial presentation, biology, the characteristics of that cancer, through how they're treated. So I don't know if we have all of the answers for that quite yet, but you can imagine if someone hypothetically had a history of receiving a lot of anthracycline chemotherapy or already having received a lot of radiation, that might impact what treatment they might receive for that secondary cancer or if they already have other existing comorbidities that need to be taken into consideration. Dr. Davide Soldato: Speaking about comorbidities, you were mentioning in the beginning that one of the focuses of this scientific work was really to try and see whether also this type of adverse health outcomes that can be potentially related to treatments were more frequent among these childhood cancer survivors. So I think that it's very interesting that for this comparison, you were able to use the data from the siblings of the patients who were included inside of the study. So, just a little bit of a comment on why you decided to use this specific methodology, which I think has a very nice touch to it when we look at these outcomes like, for example, diabetes or cardiovascular disease, and in general, do we see an increased number of chronic health conditions among survivors who were treated for childhood cancers? Dr. Rusha Bhandari: Yes, so this is a really excellent strength of the Childhood Cancer Survivor Study is that they have information, longitudinal information, on survivors as well as their siblings. So, you know, when we were discussing the design of the study, I mentioned that we have initial baseline questionnaires as well as multiple follow-up questionnaires, and that is for both the survivors and the siblings. And so we're able to really understand their health course over time. We chose to evaluate sibling data because then you're really able to look at people who have similar characteristics, right? Similar environmental exposures in theory, potentially similar genetic predispositions and makeups and things like that. And so you can really try and have as good of a comparison as possible. Dr. Davide Soldato: Did we see any increase in chronic health condition when looking at survivors compared to the siblings? Dr. Rusha Bhandari: We did. And while that's been reported before, again, I think it's important to demonstrate that in this older population when you would expect that these siblings would now also be starting to develop different health conditions. Dr. Davide Soldato: One thing that was very interesting is that when we look at the coexistence of multiple comorbid conditions and chronic condition in this population, we also see that for some of these survivors, they basically have the same rates of comorbidities as compared to siblings who are potentially 20 years older than them. So I think that there is really that striking point, as you were mentioning before, of accumulation of changes, also physiological changes that can potentially drive a higher frailty index, which was also higher when looking at these survivors compared to their siblings. One outcome that was really not that worse when we look at survivors of childhood cancer was actually mental health. And as I read the paper, it was something that really surprised me a little bit because you would imagine that going through such a harsh diagnosis, such very complex treatment, very early in their life could potentially lead to some worse health outcomes also in terms of mental health over time. But this was not seen. And just a comment on this, because I think it's a very surprising data. Dr. Rusha Bhandari: Yes, I appreciate that question. So, as you mentioned, mental health is such an important issue for patients, both those undergoing treatment as well as those in long-term survivorship. And in our study, we found that survivors were not more likely, as you mentioned, to report poor mental health compared to their siblings. And I think there's a few possible reasons for this. You know, again, this is self-reported data amongst siblings and survivors who survived to at least 50 years of age and completed a questionnaire. And so that is the group of individuals that we were able to evaluate this in, so we have to keep that in mind. But I think our findings may also reflect the resilience of this particular cohort of aging survivors that we included. This finding has been reported in other studies of survivors as well, and so I think it very well may speak to the resilience of the cohort that we're looking at. Dr. Davide Soldato: Going back just a little bit, you mentioned that the majority potentially of these survivors who were included in the current analysis were treated between 1970s and 1980s. So, as you were mentioning before, radiotherapy was seen as a significant contributor to second neoplasm and also to the increase of this chronic health condition. So, do you believe that there is still a role for these survivorship studies as we are approaching treatment modalities where radiotherapy is administered less frequently or with lower doses or omitted at all in the treatment course of these survivors? Dr. Rusha Bhandari: Absolutely. I think you mentioned a very important point, which is these findings are most applicable to the patients who were included in this cohort or similar cohorts, those who were treated in the 1970s and 80s who now are 50 years or older at this point in time. And as you know, treatment modalities have really changed. You know, as you mentioned, we'll use less radiation in many cases whenever possible, but there are so many new modalities, so many different chemotherapeutic agents, immunotherapy. There's so much more we need to learn about the long-term effects of some of these newer treatment modalities. And also, we've been able to really intensify our treatment regimens with improvements in both treatment approaches and supportive care. And so I think we have a lot to learn about those late effects, and ongoing studies are certainly needed as we continue to have this growing population of older survivors. Dr. Davide Soldato: And now a more general question which builds on the results of the study but goes a little bit beyond what was the scope of the research. So we have just discussed that there is an excess mortality in general, there is a higher risk for secondary malignancies in this population, we see higher accumulation of chronic comorbid conditions that need to be treated. So building on these results, in your opinion, what would be the best framework to follow up these patients over time? Because I imagine that for some of these patients who have been treated 30, 40 years before the moment where we see this type of events, they can be potentially also discharged from more specialistic medical care. So what is the best course of action? Should we keep all of these patients under observation in a very specialistic environment under the care of the oncologist or the pediatric oncologist? Should we create a stronger bond with general practitioners so they know that there is this problem? Dr. Rusha Bhandari: Yes, I mean, I think you're reading my mind. We thankfully do have evidence-based guidelines. We utilize the Children's Oncology Group Long-Term Follow-Up Guidelines, which include screening recommendations for secondary cancers, chronic health conditions, everything based on the underlying diagnosis and treatment that these patients received. But we recognize that a large proportion of these survivors do not continue to have lifelong follow-up at a survivorship center, but really do need that specialized screening based on their treatment that they received. And I think for that reason, it's so important that we continue to build relationships with their primary care providers and really make sure that both patients and their providers have this information at hand regarding what their treatment is and what the screening is that they need and that we be able to have this community whereby we are able to help inform the screening in our own survivorship clinics, but also help guide some of the primary care providers who are going to be seeing these patients in the long run. Dr. Davide Soldato: Do we have any data showing what is the adherence rate of these patients to this type of continuous screening and monitoring over time? Because I imagine that that might also be a point for improvement in terms of quality of care. Can we retain as much childhood cancer survivors as we want as we are learning that there are all these potential negative health outcomes over time? Dr. Rusha Bhandari: We definitely within the survivorship community do want to help make sure as many survivors as possible are being engaged, again, whether it's at their specific cancer center or whether it's in the community, recognizing that for many reasons, it's not feasible to always return to that cancer center for your regular survivorship care. I think there's a lot we can do. Going a little bit outside the scope of your question, but I think there's a lot that we can do nowadays in terms of telehealth and being able to communicate with patients and their providers even if they're geographically not located right near us. But we do have data that shows that the further out many patients get from their initial diagnosis and treatment, the less often they might follow up with a survivorship provider. Some of this varies by different treatment. Dr. Davide Soldato: So, basically the final question is that we need more education and potentially more resources for survivorship clinics and in general to better inform patients and providers about these potential long-term outcomes. Dr. Rusha Bhandari: That's certainly a focus of our survivorship program, for example, is to make sure that we're able to educate patients, inform them of their risks, and why certain screening tests are recommended at certain times in their survivorship journey. And then I think again, thankfully nowadays with all of the electronic medical records and different methods for us to communicate, there's a lot of opportunity for us to continue building these relationships with those primary care providers and making sure they have the information at their fingertips as well as to be able to work in conjunction with these patients to continue to formulate their plans and carry out these screenings and then again, like I was saying, have an easy open line of communication with the oncology centers if they do have any questions. Dr. Davide Soldato: Thanks so much. This brings us to the end of this episode. I would like to thank again Dr. Bhandari for joining us today. Dr. Rusha Bhandari: Thank you so much. It's been a real pleasure speaking with you. Dr. Davide Soldato: And we appreciate you sharing more on your JCO article titled "Health Outcomes Beyond Age 50 Years in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." If you enjoy our show, please leave us a rating and review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

DLL3 and SEZ6 Expression in Neuroendocrine Carcinomas

JCO Precision Oncology Conversations

Play Episode Listen Later Nov 19, 2025 26:59

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

Long-Term Remission After Cilta-cel in Patients With RRMM

Play Episode Listen Later Nov 13, 2025 27:31

Guest Dr. Sundar Jagannath and host Dr. Davide Soldato discuss JCO article "Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma," and the efficacy of CAR-T cell therapy in patients with heavily pretreated RRMM (relapsed/refractory multiple myeloma). TRANSCRIPT Dr. Davide Soldato: Hello and welcome to JCO After Hours, the podcast where we sit down with authors from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, medical oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO author, Professor Sundar Jagannath, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and the Tisch Cancer Institute. He also serves as Network Director for the Center of Excellence for Multiple Myeloma, and he is an internationally recognized expert in the field of multiple myeloma. Today, we will be discussing the article titled, "Long-Term Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma." Thank you for speaking with us, Professor Jagannath. Dr. Sundar Jagannath: Thank you for having me, Dr. Davide Soldato. It is a pleasure to be here. JCO is a highly recognized journal among the oncologists, so I am very happy and privileged to be here today. Dr. Davide Soldato: Thank you so much for being with us. So, I wanted to start a little bit with the rationale of the study and the population that was included in the study. So, the trial that we are discussing, CARTITUDE-1, was already published before, and we observed very good results with a single infusion of cilta-cel. So we had previously reported a median progression-free survival of 30 months, and median overall survival was not reached. So, I just wanted to ask you if you could guide us a little bit into the population that was included in the study and also explain a little bit to our listeners what is the drug that we are discussing, cilta-cel. Dr. Sundar Jagannath: It is a CAR T-cell. This is a patient's own lymphocytes, which goes through apheresis and is sent to the company, where they modify it and introduce the B cell receptor. In this case, you know, there is a heavy chain gene receptor for the BCMA, and in cilta-cel, there are actually two receptor sites on each molecule, or there are two binding domains on each receptor molecule. So, it is considered to be quite efficacious. As you reported, the earlier results that the patients who participated, 97% of the patient responded. Now, you asked about the patients who participated in the clinical trial. This clinical trial was conducted between July of 2018 and October of 2019. At that time, this was a phase 1b/phase 2 trial, and the whole idea was to take patients who had relapsed all the available treatment regimen so that these patients were considered to have, in the unmet medical need situation. So, what does that entail? That means the patient should have been exposed to a proteasome inhibitor, to an immunomodulatory molecule, and to an anti-CD38 monoclonal antibody and should have received at least three or more prior lines of therapy and should be actually progressing on their last line of therapy. So with that requirement, if you look at it, the median number of prior therapy on the patients who participated was actually six. So patients were heavily pretreated. They had exhausted all available treatment options. So, they can participate in this clinical trial. And if not, there have been real-world evidence, such as LocoMMotion, which had reported what is the outcome for such a patient if they were treated outside of this clinical trial, if they were treated with the then available regimen. Their median progression free survival would have been only 3 months, and most patients would have lost their life within a year. So, this was truly an unmet medical need with patients in a very difficult clinical situation. Let's put it that way. So, those were the patients who participated in this particular trial. Dr. Davide Soldato: Thank you very much. And as we mentioned before, the results that were obtained in this clinical trial were really very interesting. And now, in this issue of the Journal of Clinical Oncology, you are reporting data with a longer follow up. So we are actually at more than 5 years of follow up for the patients included in this trial. So, I just wanted a little bit of insight into why you decided to report these long-term outcomes and what type of information do you think you could provide with this study to the medical community? Dr. Sundar Jagannath: This is very important because this was a clinical trial that was done in patients who were, as I said, in unmet medical need. Most of the patients had prior stem cell transplantation, had gone through a proteasome inhibitor. Many of them have had both Velcade and carfilzomib treatment. Most of them had been exposed to lenalidomide and pomalidomide. And as required, all of the patients had to have had prior exposure to anti-CD38 monoclonal antibody or daratumumab. So, the patients were heavily pretreated. Typically, TIL CAR T-cells came into the field at this particular moment, until then, we were developing small molecules, and they usually would have a PFS of 3 months and median life expectancy of a year, the overall response rate of 30%, and that is how, if you look back, that is how carfilzomib was approved, that is how pomalidomide was approved. So, the drugs which were approved, including daratumumab, you know, the response rate was in the same ballpark. So you would see that most agents, single agents, would have had a response rate in the neighborhood of 30%, the progression-free survival would have been between 3 to 5 months or 6 months at the most, and the life expectancy was short. And here comes a drug, and when I was following the patients at Mount Sinai, I found that there were a subset of patients, they got one-time treatment and they were in complete remission, no trace of cancer with annual evaluation with PET CT and bone marrow evaluation for MRD. So, I said this is remarkable, and this needs to be reported. And I went to the Janssen and company, and they agreed to review the entire experience. This is remarkable that 32 of the 97 patients, or one third of the patients, were alive and progression-free. This is unheard of for any clinical trial until now, that the patient will be progression-free, one third of the patients on a clinical trial will be progression-free, in the late stage of their disease. So that is the most important impact. And that is why this 5-year follow-up results were presented. Dr. Davide Soldato: Thank you very much. That was very clear. And as you said, we are speaking about a population that was heavily pretreated, that had exhausted all type of treatment options outside of a clinical trial. And as you said, one third of the patients was alive and progression-free after 5 years from being included and infused inside of the study. So, considering this population that, as we said, had received all treatment options, I was wondering if you observed any kind of differences in terms of disease characteristics when looking at these patients that had exceptional response, so, alive and progression-free at 5 years, and the patients that sadly had developed a progression after the infusion in the study. Dr. Sundar Jagannath: This is very important because we wanted to see who are the patients who are having this exceptional outcome. And we looked at all the 97 patients. If we look at all the patients, we saw that there were initially, out of the 97, 17 patients died earlier in the disease course due to treatment related complications, etc. But there were about 46 patients who had progression of disease and 32 patients, or one third, were alive without progression of disease. Then we looked at the 46 patients who had progression of disease. Of them, we found that 30 had disease progression and its complication, and there were actually 13 patients who were still alive even after progression of disease. So we decided to compare these 46 patients who had progression of disease versus 32 patients who had no progression of disease to see what is the difference. To our surprise, the age was similar, male, female distribution was similar. High-risk cytogenetics, which we would have thought, you know, that is why we say high-risk disease, the term, high-risk cytogenetics was equally distributed. That was really a surprise. Number of lines of prior therapy, number of exposure to drugs, all of that was the same. So that was also interesting. But a theme did emerge. Patients, in general, tend to have lower burden of disease who had the exceptional outcome. But there is one which we considered as bad, the extramedullary disease. Multiple myeloma being a blood cancer, it is usually in the bone marrow. When it starts growing outside of the bone marrow, the extramedullary disease, usually it portends poor prognosis. But we were surprised that actually there were an equal number of extramedullary disease patients even in the long-term survivor as those who had progressed of disease. So the most important takeaway was patients who had lower burden of disease, they had less number of myeloma cells in their bone marrow, percentage wise, and the soluble BCMA level was lower. Soluble BCMA is an indirect measure of the amount of plasma cells in the patient's body. It is like a tumor burden. So they were low. So, this was an important finding because it has future ramification, as you can understand. If this treatment is made available earlier in the disease course of the patients, where we are able to control the disease better, then more patients are likely to have such wonderful outcomes as one third of the patient experience in the late stage of the disease. Dr. Davide Soldato: So, you already mentioned soluble BCMA as a marker of potentially better prognosis as being correlated to a lower volume of disease. I was wondering if you could give us some more information about the biomarkers that you evaluated in the study. For example, you evaluated a little bit the CAR T expansion kinetics and also some others that I think could be interesting and could point to some population that experienced such important benefit. Dr. Sundar Jagannath: That is a very important point because CAR T-cell, it is a live cell and its efficacy depends upon how well the CAR T-cell is going to function. And then, you know, the patient undergoes apheresis. This is a patient's own lymphocyte. So first and foremost is who would generate good CAR T-cell. Those who have plenty of lymphocytes at the time they are coming for apheresis. This is likely to happen earlier in the course of the disease than in patients who have gone through numerous lines of therapy and exhausted. So, in this particular trial, of course this was in late stage of the disease, and so we were able to show patients who had lower number of T cell in circulation, and the way to measure is if they had more neutrophils and less lymphocytes. So that is what is called as a higher T cell over neutrophil, they did better. If they have more neutrophil than T cells, then they did not do well. So, procurement. The second one is also whether the T cells are more naive, you know, not exhausted T cells. So more naive T cells, if you are able to procure from the patient, they did very well. Now, after the CAR T-cell manufacture, then the expansion, when you put it back into the patient, if the T cells expand very well, so that the effector, that is the CAR T-cells to the tumor ratio is good, so there are more effector cells, the CAR T was able to expand and the amount of tumor was less, then the efficacy was very, very good. As I said, the patients in this group, those who had a lower burden of disease, they did better, and that is because of the CAR T-cell expansion, so the effector to the target ratio was favorable. So that is another important. And then there are also the type of CAR T-cells, having CD4 T cells with central memory phenotype at the peak expansion also makes a difference. So all of that matters. But this is important because the efficacy of the CAR T-cell, it is persistent, long persistent and keeping the cancer down. Its ability to get rid of the cancer completely at the first go around because usually we are not able to detect the CAR T-cells beyond 6 months in the majority of patients and very rarely after a year or two. So it is very uncommon to find the CAR T-cells in circulation or even in the regular bone marrow evaluation. So, efficacy, the expansion, having naive T cells, having good effector to target ratio and more central memory kind of T cell, because if it is all effector T cell, they will get quickly utilized and get exhausted, whereas the central memory cells can expand more and give more effective CAR T-cells. Dr. Davide Soldato: Thank you very much. I was wondering if you could guide us a little bit into what is your opinion regarding the positioning of CAR T-cells given all of these logistics that is necessary compared, for example, with bispecific antibodies against BCMA, which have the same target, but they do not have all of these logistics before being administered to the patient. Dr. Sundar Jagannath: That is a very important question, how to sequence these treatments now that we have two BCMA-directed CAR T-cells available. We have three BCMA-directed bispecific and one GPRC5D-directed bispecific antibodies are available. And so the question comes in for at least the currently approved CAR T-cell therapy, there is an obligatory time. You have to go through apheresis and you have to ship to the company, and there is a manufacturing time, roughly about 2 months before they can receive it. During that time, you want to make sure the patient's disease is under control. So that is a given. There are several ways to look at it when we evaluate the patient and talk to the patient. One good thing is now the two CAR T-cells which are approved, one is cilta-cel we talked about, and the other one is ide-cel. Ide-cel is approved in earlier line of therapy, two or more prior lines of therapy, and cilta-cel is approved in patients who have failed one line of therapy and who are lenalidomide refractory. So, the treatment of CAR T-cell is available earlier. And as I said, when you administer CAR T-cell earlier, you are able to keep the disease burden down, and it is a one and done deal. There is a better quality of life for the patient, and you are able to produce long, durable remission and potentially a cure. Now coming to the bispecific, they are currently available in later lines of therapy. So if you look at it from a patient's perspective, you can use the CAR T-cell earlier and then go through the bispecific therapy. But if the patient comes with relapsed refractory myeloma and has not used the CAR T-cell therapy and has not used the bispecific therapy, then the physicians have to decide which one they want to use. If somebody's disease is rapidly progressing and they need immediate tumor reduction and they have already exhausted all available therapy, then going through BCMA bispecific therapy is quite appropriate. And secondly, CAR T-cell therapy is generally given to somewhat physically more fit patients, whereas bispecific therapy, because you are giving antibody at step-wise dosing in this patient, and you have the ability to stop at any particular dose and then come back and redose, whereas CAR T is, you just give it to them one time, you have a lot more control. So intermediate frail or even frail patients can go through bispecific therapy, whereas it would not be in the best interest of the patient to go through a CAR T-cell therapy when they are frail. So that is another important point. But from the information available, when the patient goes on a BCMA bispecific therapy and they start progressing on treatment, usually it is their T cells are exhausted or the BCMA is no longer expressed on the tumor cells. So coming with CAR T-cell later on is usually not effective, whereas giving CAR T-cell earlier, if the patient relapses later, they have good T-cell function and most of the time the BCMA is still expressed. So you are able to give the BCMA to the maximum benefit by using the CAR T first and BCMA later. So if somebody asked me how to sequence this, just off the bat, you will say CAR T first, BCMA bispecific second. But as I said, there are unique situations. Then there is another potential that is happening. You can change the target. You can use a BCMA against GPRC5D to reduce the tumor, and then go ahead and consolidate it with a CAR T-cell therapy. That is also possible. You are changing the target from GPRC5D to BCMA, the tumor is already down, so the patient is likely to benefit. So these are all newer treatment options which have become available to the physician. So they will have to look at individual patients and decide what is the best course of action for that patient. Dr. Davide Soldato: So, I just wanted to close a little bit with your opinion about how these results translate into clinical practice. So considering this outstanding 5-year data that we have seen, one third of the patients who are alive and progression-free after a single infusion of cilta-cel, do you think that we could start to think about functional cure even in patients who have a diagnosis of relapsed refractory multiple myeloma? Dr. Sundar Jagannath: My feeling is this is important because in this particular study which is published, 12 patients who were followed at Mount Sinai out of the 32 patients who are alive and progression-free, 12 were followed at Mount Sinai. And they were evaluated every year with bone marrow MRD testing by clonoSEQ in 11 of the 12 patients, and one was by multiparametric flow cytometry. So most of them were 10 to the minus 6, not even one in a million cancer cells, and all of them had functional imaging, which is called PET CT every year. So these were patients who had no evidence of disease that we could detect with the technology available today, serologically, in the bone marrow, or anywhere else in the body with a PET CT. They were found to be disease free after a single infusion of cilta-cel. So, that would be almost to the definition of a cure because if you look at cure as a definition for any cancer, cure is defined as a state of complete remission with no trace of cancer that persists over a period of 5 years or longer without maintenance. And that will be applicable for breast cancer, lymphoma, leukemia. So it is a general statement. And if we use that in myeloma too, then I could say that these 12 patients from my center, we proved that they are cured of their myeloma. They are not functionally cured. You've got to remember, there is only cure. That was the definition across all diseases. So there is nothing like a functional cure. They are cured of myeloma. So is myeloma curable? This is the first time we are looking at that. We do know, every physician treating myeloma that there are patients out there, 10 year and beyond, without evidence of disease. This has been published by University of Arkansas, Bart Barlogie's group, who has been saying that myeloma is a curable disease for a long time. And many others have shown long-term follow up. But this one in a late stage disease, we were able to show that they were one treatment with no maintenance. All other studies have been in newly diagnosed myeloma patients. Nobody has shown in late relapse patients on a clinical trial a third of the patient will be progression-free. And 12 of them who were studied were actually disease free. So they were cured of the disease. So if we accept that, then the next question is, first step towards cure is achieving complete remission. They should have no monoclonal protein by any technology you want to use, no measurable residual disease using next gen sequencing or clonoSEQ, and functional imaging whole body PET CT or whole body MRI. So that is important, definition of the complete remission. And then it has to be sustained. That is something the IMWG and IMS, International Myeloma Society, they will have to come together for a consensus. How many years should they be followed and should be in this kind of status with no trace of cancer? Is it, 3 years are enough? 4 years enough? 5 years is enough? For me, I said in this paper, 5 years is a good definition for achieving a potential cure. Then you use the term 'functionally cured'. I have a problem with functionally cured and operationally cured or whatever. Functionally cured was originally put out by Paiva from Spain. There were 8% of newly diagnosed myeloma patients who have, after they go get treated, they will have an MGUS like phenomenon, a small amount of paraprotein detectable, and they are only 8%. And he said that these patients could be off treatment and the disease does not progress. But the problem is when you are giving treatment like maintenance therapy continuously until progression, you do not know exactly who is in the MGUS situation. So you have to have done sophisticated flow cytometry like Paiva did, and it is not quite clinically applicable. So functionally cured applies only for 8% of the people, so it should go out of the vocabulary. Then you can say 'operationally cured'. These are the patients traditionally Bart Barlogie and others showed that they have a large number of patients who have been followed for 10 years with no recurrence of disease, not on treatment. But in those days, they did not have MRD PET CT and all of them done systematically. So that is why they had to come up with a situation where they said they were operationally cured. So yes, myeloma patients have been cured since auto transplant was introduced. I completely agree. It is not new to the CAR T-cell therapy. But the beauty of the CAR T-cell therapy was it was in relapsed refractory myeloma, unmet medical need, number one. Number two, they were studied systematically. It was a clinical trial adjudicated by FDA and EMA for drug approval, cilta-cel was approved. So these patients were carefully followed, and it was a multi-center study. And in that group of patients, we were able to show patients- So, I think this would indicate cure is a reality in myeloma, and as these kind of treatments, immunologic treatment, either it is a CAR T-cell therapy or BCMA bispecific or whatever, there is a chance more patients are likely to be cured, and these treatments have to move forward and so that we are looking towards a cure. That is the beauty of it, and I just thank you for asking and also throwing in this so-called functionally cured, which people like to use casually, and I say it is time to talk more cure and not stuck with functionally cured because that does not allow the field to progress. Dr. Davide Soldato: Thank you very much. That was very interesting. Dr. Sundar Jagannath: And provocative. Dr. Davide Soldato: A little bit, but I think that we needed to close the podcast with this kind of reflection coming from someone who is an expert in the field, as you are. So, I really wanted to thank you for joining us today and for sharing more on your article, which is titled, "Long-Term Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma." If you enjoy our show, please leave us a rating and a review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. Dr. Sundar Jagannath: Thank you. 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.

The Man at the Bow: Remembering the Lives People Lived Prior to Cancer

Play Episode Listen Later Nov 11, 2025 26:28

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

Lymphedema in Cancer Care with Maureen McBeth

Oncology Overdrive

Play Episode Listen Later Oct 30, 2025 34:46

In this episode, host Shikha Jain, MD, speaks with Maureen McBeth, PT, MPT, CLT-LANA, about understanding individualized patient experiences with lymphedema, the value of exercise oncology and more. • Welcome to another exciting episode of Oncology Overdrive 0:14 • About McBeth 0:23 • The interview 0:52 • How did you end up in the lymphedema and cancer rehab space? 1:31 • Why is lymphedema such a big topic, especially in the breast cancer space? 3:20 • Jain and McBeth on the complexities of individual lymphedema cases, including studies on lymphatic imaging. 5:25 • Do you feel like there have been advancements in the lymphedema space that can improve our understanding of it? 9:43 • Have stigmas around lymphedema evolved over the years? 12:31 • McBeth on the educational materials available to physicians surrounding cancer-related lymphedema and prospective surveillance. 15:15 • Tell us about ImpediMed and its purpose. 17:06 • How do you incorporate these technologies into the current dialogue about more holistic care? 21:27 • Jain and McBeth on exercise oncology and its impact on overall survival. 24:22 • In ten years, what would you envision as the future of lymphedema and exercise oncology? 29:01 • If someone could only listen to the last few minutes of this episode, what would you want listeners to take away? 32:31 • How to contact McBeth 33:33 • Thanks for listening 34:20 Maureen McBeth, PT, MPT, CLT-LANA, is a licensed physical therapist and certified lymphedema therapist with over 25 years of experience in oncology rehabilitation, clinical education, and patient advocacy. She currently serves as senior medical affairs liaison at ImpediMed. We'd love to hear from you! Send your comments/questions to Dr. Jain at oncologyoverdrive@healio.com. Follow Healio on X and LinkedIn: @HemOncToday and https://www.linkedin.com/company/hemonctoday/. Follow Dr. Jain on X: @ShikhaJainMD. McBeth can be reached via email mmcbeth@impedimed.com. Learn more about ImpediMed at https://www.impedimed.com/, or follow them on LinkedIn or Instagram @impedimedhealth. References • Pasket ED, et al. J Clin Oncol. 2012;doi:10.1200/JCO.2012.41.8574 • Schmitz KH, et al. J Natl Cancer Inst Monogr. 2025;doi:10.1093/jncimonographs/lgaf007. • Stout NL, et al. Cancer. 2012;doi:10.1002/cncr.27476. Disclosures: Jain and McBeth report no relevant financial disclosures.

cancer md jain cancer care mpt lymphedema mcbeth jco j clin oncol shikha jain clt lana

Reflection: When Cancer Affects a Family Member

Medscape InDiscussion: Multiple Myeloma

Play Episode Listen Later Oct 30, 2025 20:49

Listen to JCO's Art of Oncology article, "Reflection" by Dr. Jamie Riches, who is an Assistant Professor at Columbia University and Director of the Hematology Oncology Hospitalist Service. The article is followed by an interview with Riches and host Dr. Mikkael Sekeres. Dr Riches shares a deeply personal narrative, reflecting on the profound personal and professional impact of losing her young family member to cancer, illuminating the intimate intersection of grief, loss, and healing. TRANSCRIPT Narrator: Reflection, by Jaime C. Riches, DO If I stand this way, with my shoulders back, my chin lifted, if I hold my breath for a moment, my skin fits my bones just right. Each subtle motion is an effort to make my clavicle more prominent, to manifest my ribs. I feel so ignorant about beauty. I was at the side of her hospital bed as she uncovered herself and asked me to look away. Her eyes, glassy and hollow, met mine. "I'm so ugly right now." It's an interesting piece of practicing medicine, to be an observer of bodies, their look, their feel, and their function. Which lines are strength and which are fatigue…which ones are scars and how they have healed. My words were soft and aching, "You are beautiful" I said, knowing that her skin fits her bones too tight. They are almost all that's left. My 38-year-old cousin's oncologist is my colleague, my friend. When she was diagnosed, he reminded me that there were excellent treatments available. I reminded him that none of them would allow her to see her children start kindergarten. Redefining excellence, I thought, sounded like a cancer center's marketing strategy that just missed the mark. As I looked away, a piece of me splintered. It isn't the same when it's someone you know, when it's someone you love. Maybe I feel shame for underappreciating my own fertile marrow, my fat and muscle, and my own existence. Maybe it's guilt for dedicating my whole life to work that can't save her, for being the one to look her mother in the eye and say she can't be saved. Maybe, just sadness. This lonely world, that only exists right at the bedside, is like a magically devastating song and I am humming the rhythmic asynchrony of being a doctor, and just being. "From where do we yearn?," I wonder. It's from within these little spaces we look to fill the absence of something beautiful. The moments that we're longing to be a part of. We are all mothers—the seven of us now in her room, aunts and cousins united by a last name—by the successes and losses we previously thought unimaginable. We've known the brittle anticipation of a new life, the longing, the joy of spending time, and the sense of simply existing in these spaces. We are the daughters and sisters of firefighters. We are women who know the low bellow of the bagpipes, women who own "funeral clothes." We've tried to disinherit the same shades of blue, and all of our distance has brought us right here, where they're making her comfortable. She knows that her time has been spent. Her eyes are the color of her favorite flower, a yellow rose, and her once sterile room appears almost sunlight by the garden of bouquets. Her mother is sitting by her side, gently moving her fingers across what would be a hairline, the way you would touch a newborn in those moments when you're just realizing you didn't know you could love someone so much. There's a song running through my head, "Golden Slumbers" (The Beatles, Abbey Road, 1969). Even playing in my memory, it gives me chills, starting right beneath my jaw and circulating through my limbs. Once, there was a way To get back homeward Once, there was a way To get back home Sleep, pretty darling, do not cry And I will sing a lullaby Nothing illustrates the frailty of existence like a mother preparing for her inevitable goodbye. Once you see it, you can be certain that biology is imperfect. We're convinced that we're grieving throughout the whole of motherhood, as our babies become grown people of their own, as they live their lives. But it isn't grief. We're simply living a life that is singular, in a series of moments that are final. "Golden Slumbers" doesn't actually seem to end. It just subtly transforms into the next track as if they were one, and before the chills are fully absorbed, you're struck by something totally new…triumphant trumpets. When her breath stopped, it wasn't held. I don't think she realized the bravery it took to leave this world with such grace, to be unlonely. I've been witness to so many punctuated pulseless yawns, but not this one. I wish I knew by which of these wounds am I softened and by which I am hardened, but I don't. They heal, with secondary intention, naturally and slowly, from the inside out. Mikkael Sekeres: Welcome back to JCO's Cancer Stories: The Art of Oncology. This ASCO podcast features intimate narratives and perspectives from authors exploring their experiences in oncology. I'm your host, Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. Today, I am so thrilled to be joined by Jamie Riches, who is Assistant Professor at Columbia University and Director of the Hematology Oncology Hospitalist Service. We'll be discussing her absolutely gorgeous article, "Reflection." At the time of this recording, our guest has no disclosures. Jamie, I want to thank you so much for contributing your essay to the Journal of Clinical Oncology, and welcome you to discuss your article. Jamie Riches: Thank you so much for having me. Mikkael Sekeres: I have to say, I was so moved by this and just loved the writing. I don't drop the 'G word', gorgeous, very often when describing pieces, but this was truly moving and truly lovely. Jamie Riches: Thank you. Thank you so much. It was a really deeply personal story to me. Mikkael Sekeres: So I wonder if you can tell us a little bit about yourself. Where are you from, and walk us through your career? For example, where did you do your training? Jamie Riches: Well, I am from Brooklyn, New York, and I did my training at an osteopathic medical school in Harlem called Touro, and my residency training at what used to be called St. Luke's-Roosevelt, and now is Mount Sinai West after many of the New York City mergers. I did a chief resident year at Memorial Sloan Kettering and started my oncology hospitalist career there for many years and have been at Columbia now for three years. Mikkael Sekeres: Wonderful. Isn't it interesting how the institutions of our youth are no longer, and that seems to happen at a faster and faster pace? Jamie Riches: I know. I feel the need to reference the old name sometimes when I'm discussing it. Mikkael Sekeres: Can you tell us a little bit about your own story as a writer? How long have you been writing reflective or narrative pieces? Jamie Riches: I have probably always been a jotter. I think that's for as long as I can remember, and I've enjoyed that process. And I think once I was an undergrad, I studied chemistry, I majored in chemistry, but I really filled up a bunch of elective time with writing classes and learning what I could about the processes of writing. And I guess almost 10 years ago now, I enrolled in the graduate certificate program in Narrative Medicine at Columbia. And that program helped me explore a little bit in terms of form and function and in terms of really relating my writing to my own personal experience as a physician. Mikkael Sekeres: And if I'm not mistaken, the field of narrative medicine was really in part born at Columbia, wasn't it? Jamie Riches: It was. Yeah. Rita Charon was the founder of the practice as a field, yeah. Mikkael Sekeres: And what was it that that experience- what did the formal training teach you that you couldn't have figured out on your own by the iterative process of reading and writing? Jamie Riches: I think there's something to having a group of people critiquing you that really allows you to become better in any field, in any practice. And I think there's something to having a, you know, a relatively safe space to explore different ways of doing something. For example, writing poetry, which I really hadn't done much of before and have done a bit of since. I think having a space where there are both educated critics and experts being able to look at your work and say, "This is working and this isn't," was really helpful for me. Mikkael Sekeres: You know, I've heard with writing, the notion that your first critics should be people you trust and feel as if you're in a safe space with because you're so vulnerable with writing. Even exposing it to relative strangers in a formal course can be, I don't want to use the word damaging, but I guess damaging, or at least get you out of a safe space that you need for writing. Do you have an inner circle that you trust for your writing? Jamie Riches: I do. I do. Mikkael Sekeres: If you feel comfortable doing so, can you tell us what prompted you to write this piece? Jamie Riches: This piece just sort of came out. This piece is real, and it's a real experience, and the processing of this experience has happened on so many different planes for me, and writing is really one of them. And once I sat down and said, "Let me write some of this down," it just kind of poured out. Mikkael Sekeres: Sometimes we write to process. I once heard somebody say that writing is the only time in life when you get a free redo, right, or a do over. We say something or we post something on social, and it's out there in the universe. But with writing, it's very personal, and we can look at a paragraph or a sentence and say, "Gee, that just doesn't feel right," and rework it if it's not communicating exactly what I was hoping it would. The other aspect of writing, of course, is that it allows us to ruminate on something that's just occurred and to try to make sense of it. Do you think that was some basis for writing this? Jamie Riches: I think so. And I think maybe just relating one really specific experience into the greater realm of the work that we do every day, and how that experience both stood on its own, but also is woven into so many other patient encounters and encounters with families. And that's a form of processing, I think, for sure. Mikkael Sekeres: Can you tell us in your own words about the main character in this piece and what was going on? Because you write it in a lovely way that allows the reader to discover what's transpiring gradually, but if you could tell us in your own words, who is this person? Jamie Riches: Yeah. So the person that I'm talking to in some parts of the story and talking about in much of the story is my cousin, Patrice, who was diagnosed with bladder cancer at 38 years old and who has had interactions with the medical field as a patient but is not a physician, is not a medical professional, and so had a lot of questions and a lot of trust and reliance on those of us in the family who had some medical knowledge and experience. And so I wound up being pretty intimately involved in her care as a family member, and that was really a fine line in a lot of ways because my friends and colleagues were the care team, and I was the family member. And many of us have been in that position in many different ways, but it's always a fine line. And she was young, and she was very positive throughout really the course of her illness. She had twins who were two years old at the time of her diagnosis. And I think, I'm a little bit speechless now, as you can see, I think she just was so incredibly graceful, and I think I used this word in the story, throughout the entirety of her illness, which included multiple lengthy hospitalizations where she had spent time away from her children. And I still don't know how she did it with the patience and the thoughtfulness and the love for everyone else that she did. Mikkael Sekeres: You really honor her in this piece and paint such a beautiful portrait of her. In the essay, you write, "It's an interesting piece of practicing medicine to be an observer of bodies, their look, their feel, their function. Which lines are strength and which are fatigue, which ones are scars and how they've healed." It's a beautiful couple of sentences. In this case, you aren't really playing the role of doctor, are you? Can you talk a little bit more about when that line's blurred between being a family member and and the practice of medicine when people are relying on you to help out with their medical care? Jamie Riches: Yeah, I think most of us know this gray area fairly well, and the gravity of the situation really dictates how blurry the line is. And it's true, I wasn't the doctor in this situation, and I had as much information about the scans and the clinical picture and the day to day trajectory and the lab results and the toxicity profiles and the data from the studies that the regimens were approved based on. And that made it impossible to step out of the doctor role or mentality, and I also wasn't making the formal recommendations by any means, but I think it's hard to sort of exempt yourself from that space once you're in it. Mikkael Sekeres: Yeah. I think we also sometimes don't realize how even the smallest contribution we have in advising somebody about their medical care becomes very, very meaningful and how much those words can have an effect on somebody. I recall my uncle was diagnosed with acute leukemia, so that's right in my bailiwick, of course. And I remember talking with him about transplant and being as neutral as humanly possible about whether he should proceed with the transplant given the characteristics of his leukemia. And months later, after he had gone through the transplant, he said, "You know, I went through this even though you really advised me not to." So as neutral and trying not to sway someone and giving advice as we are, people hear us differently. Did you find that also with your cousin? Jamie Riches: I did. I phoned into one of her oncologist appointments, and her oncologist, who I have to say is wonderful and who I have the utmost respect and really love for, who took great care in taking care of her, went through in detail everything they could about her disease and about treatment options and really explained everything, and took a minute and said, "Okay, do you have any questions?" And my cousin said, "No, whatever Jamie thinks." So I said, "Okay, well, we'll chat a little bit later." But that made me realize, which I think I just hadn't before, how much having an opinion matters. Mikkael Sekeres: Yeah, and that it's a gift to people when they can cede some of that decision making or some of that knowledge to somebody else and feel as if they don't have to take it on themselves. Jamie Riches: Yeah. Mikkael Sekeres: I want to read one other quote from your piece. I could just reread the whole piece, I enjoyed it so much and keep quoting it. You write, "We've known the brittle anticipation of a new life, the longing, the joy of spending time, the sense of simply existing in these spaces. We are the daughters and sisters of firefighters. We are women who know the low bellow of the bagpipes. Women who own funeral clothes." There's a lot that swims beneath the surface, I think, in that quote, that family members get together at births and deaths, that these become the occasions for the family to get together, that we put on uniforms for them, and that they happen frequently enough that we actually own the uniform to be part of them. Is that what defines us as families? Is that what we've come to? Or how about us as physicians? We own uniforms as physicians also. Are the gatherings, the only gatherings we have with our colleagues at tumor boards when we discuss successes and failures of our patients? Jamie Riches: That's a great question and a great reading, and thank you for these questions. I think every family is different, obviously, and I won't speak for the masses here, but there is a bit of a structure to the events that you're expected to attend and that you're expected to not be absent for, to sort of show up for. And those events are sort- you're right, you know, births and funerals and weddings, and they have a bit of a code to them. And as physicians, it's interesting to think about things like tumor board as the gathering spaces, because although as colleagues we're not families, we are the closest thing to going through some of these moments together. And I think these moments at the bedside, and I use that term so often because I work in the hospital, and I am literally often sitting in a hospital bed holding someone's hand, talking to them. Those are the moments that we feel. We feel them in our bodies. I can feel it right here, and I'm touching my chest when I say that. I don't get that same visceral feeling from looking at most scans, looking at most lab reports, or even having academic conversations with people. And I think that you're right, things like tumor board or even other academic conferences really are the gathering spaces for physicians, but that makes me question if those are the spaces that matter most. Mikkael Sekeres: I think that's a great point also to end our time together. It has been such a true, true pleasure to have Jamie Riches on our JCO Cancer Stories podcast to talk about her gorgeous piece, "Reflection." Dr. Riches is Assistant Professor at Columbia University and Director of the Hematology Oncology Hospitalist Service. Thank you so much again for submitting your piece to us. Jamie Riches: Thank you so much. Mikkael Sekeres: And thank you to our listeners for choosing JCO Cancer Stories: The Art of Oncology. If you've enjoyed this episode, consider sharing it with a friend or colleague or leave us a review. Your feedback and support helps us continue to have these important conversations. If you're looking for more episodes and context, follow our show on Apple, Spotify, or wherever you listen and explore more from ASCO at asco.org/podcasts. Until next time, this has been Mikkael Sekeres. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show notes: Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr Jamie Riches is an Assistant Professor at Columbia University and Director of the Hematology Oncology Hospitalist Service.

S2 Episode 4: Should You Treat Smoldering Multiple Myeloma?

Play Episode Listen Later Oct 22, 2025 24:51

Drs Joseph Mikhael and Peter Voorhees discuss considerations for treating smoldering multiple myeloma, including recent studies and shared decision-making. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002716. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Observation or Treatment for Smoldering Multiple Myeloma? A Systematic Review and Meta-Analysis of Randomized Controlled Studies https://pubmed.ncbi.nlm.nih.gov/40419473/ Monoclonal Gammopathy of Undetermined Significance https://www.ncbi.nlm.nih.gov/books/NBK507880/ From Criteria to Clinic: How Updated Slim CRAB Criteria Influence Multiple Myeloma Diagnostic Activity https://ascopubs.org/doi/pdf/10.1200/JCO.2024.42.16_suppl.7556 International Myeloma Working Group Risk Stratification Model for Smoldering Multiple Myeloma (SMM) https://pubmed.ncbi.nlm.nih.gov/33067414/ Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/39652675/ Lenalidomide-Dexamethasone Versus Observation in High-Risk Smoldering Myeloma After 12 Years of Median Follow-Up Time: A Randomized, Open-Label Study https://pubmed.ncbi.nlm.nih.gov/36067617/ Long-Term Outcome With Lenalidomide and Dexamethasone Therapy for Newly Diagnosed Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/23648667/ CD38-Directed Therapies for Management of Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/34235096/ Fixed Duration Therapy With Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone for High Risk Smoldering Multiple Myeloma – Results of the Ascent Trial https://ashpublications.org/blood/article/140/Supplement%201/1830/492739/Fixed-Duration-Therapy-with-Daratumumab Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (Krd) Followed by Transplant, Krd Consolidation, and Rd Maintenance https://pubmed.ncbi.nlm.nih.gov/39038268/ Early Safety and Efficacy of CAR-T Cell Therapy in Precursor Myeloma: Results of the CAR-PRISM Study Using Ciltacabtagene Autoleucel in High-Risk Smoldering Myeloma https://ashpublications.org/blood/article/144/Supplement%201/1027/531466/Early-Safety-and-Efficacy-of-CAR-T-Cell-Therapy-in

management treat treatments relevant transplants supplement efficacy meta analysis systematic review multiple myeloma medscape smoldering dexamethasone car t cell therapy jco carfilzomib

Ep. 267 Sequencing Therapies in NMIBC Management with Dr. Mark Tyson and Dr. Suzanne Merrill

BackTable Urology

Play Episode Listen Later Oct 21, 2025 59:51

New FDA-approved therapies for BCG-refractory non-muscle invasive bladder cancer (NMIBC)–where do they fit in the treatment algorithm, and how do you administer them? This installment of the 2025 NMIBC Creator Weekend™ series features host Dr. Bogdana Schmidt, assistant professor of Urologic Oncology at the University of Utah, and leading urologic oncologists Dr. Mark Tyson from Mayo Clinic Arizona and Dr. Suzanne Merrill from Colorado Urology.---This podcast is supported by:Ferring Pharmaceuticalshttps://www.ferring.com/home-classic/people-and-families/uro-uro-oncology/bladder-cancer/---SYNPOSISThe discussion delves into the newest treatment strategies and FDA-approved therapies for non-muscle invasive bladder cancer with an emphasis on BCG-refractory patients. They highlight their approaches to sequencing therapies, the real-world applicability of these treatments, and the impact of patient factors in clinical decision-making. The panel also explores emerging trials and innovative treatment mechanisms, emphasizing the importance of personalized care in oncology.---TIMESTAMPS00:00 - Introduction05:09 - Challenges and Strategies in Treatment10:55 - Bladder Sparing Therapies21:41 - Practical Tips for Therapy Administration30:39 - Challenges and Considerations in Reinduction37:05 - Clinical Trials and Future Directions44:11 - Counseling Patients on Treatment Options57:36 - Concluding Thoughts and Future Outlook---RESOURCESCORE-008 Clinical Trial https://www.sciencedirect.com/science/article/abs/pii/S1078143924010147Legend Clinical Trial:https://ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.802CISTO Studyhttps://pubmed.ncbi.nlm.nih.gov/37980511/

university strategy challenges management utah fda considerations practical tips clinical trials therapies bcg sequencing jco urologic oncology mayo clinic arizona nmibc

Whispers After the Cure: Reflections on Marriage and Malignancy in India

Play Episode Listen Later Oct 9, 2025 23:39

Listen to JCO Global Oncology's Art of Global Oncology article, "Whispers After the Cure: Reflections on Marriage and Malignancy in India” by Dr. Vangipuram Harshil Sai, who is a fourth semester medical student at All India Institute of Medical Sciences. The article is followed by an interview with Harshil Sai and host Dr. Mikkael Sekeres. Sai shares his personal reflection of a visit which transformed into an education in silence, stigma, and the unseen aftermath of survivorship for young women in India. TRANSCRIPT Narrator: Whispers After the Cure: Reflections on Marriage and Malignancy in India, Vangipuram, Harshil Sai A Summer Afternoon and A Story That Stayed The summer break of my fourth semester of medical school offered a fleeting reprieve from the relentless immersion in textbooks and caffeine-fueled study sessions. I had envisioned a few weeks of rest—a pause from the algorithms of diagnosis and the grind of multiple-choice questions that had become my daily rhythm. But one humid afternoon altered that plan. I accompanied my mother—a senior medical oncologist—to her clinic in a Tier 2 city in Southern India. Over the years, I had seen her not just as a clinician but as a quiet force of empathy. She was one of those remarkable physicians who listened not just to symptoms but also to stories. Her practice was rooted in presence, and her calm resilience often made my academic anxieties seem trivial. I settled into a corner chair in the waiting area, where the air was tinged with antiseptic and that uncomfortable waiting room stillness—an alert hush between uncertainty and news. Patients waited in quiet constellations: a man turning the same page of a newspaper, a teenage girl watching her intravenous drip as if it held answers, and a couple clasping hands without meeting eyes. It was in this atmosphere of suspended quiet that Aarthi entered. She was a young woman whose presence was composed yet tentative. Her story would become a quiet inflection point in my understanding of medicine. She was 24 years old, embodying the aspirations tied to a recent engagement. A postgraduate in English literature and a practicing psychologist; she carried herself with a rare blend of intellect, poise, and cultural grace that, in the eyes of many families, made her a deeply desirable bride. Her sari was immaculately draped, her posture measured and calm, yet in the way her fingers intertwined and her eyes briefly lowered, there was a trace of vulnerability—a shadow of the turmoil she carried within. She came alone that day, stepping into the waiting room with a composed demeanor that only hinted at the weight she bore in silence. What began as a day to observe became the beginning of something far more enduring: a glimpse into how healing extends beyond treatment—and how survival, though silent, often speaks the loudest. The Diagnosis That Changed the Wedding The consultation was precipitated by a clinical presentation of persistent neck fullness, low-grade fevers, and drenching night sweats, which had prompted a fine-needle aspiration before her visit. The atmosphere in the room held an implicit gravity, suggesting a moment of significant change. My mother, with her characteristic composure, initiated a diagnostic process with a positron emission tomography-computed tomography and biopsy. As usual, her steady presence provided reassurance amid the uncertainty. A week later, the diagnosis of classic Hodgkin lymphoma, stage IIB, was confirmed. Rapid initiation of ABVD chemotherapy would provide an almost certain pathway to remission and an excellent prognosis. Yet, this clinical assurance did not extend to personal tranquility. Aarthi made a deliberate choice to share the diagnosis with her fiancé—a considerate and empathetic individual from a well-regarded family. Their wedding preparations were already underway with gold reserves secured and a vibrant WhatsApp group of 83 members chronicling the countdown to their big day. Shortly thereafter, a prolonged silence settled, eventually broken by a call from a family member—not the fiancé—indicating that the family had decided to terminate the engagement because of apprehensions about future stability. The union dissolved without public discord, leaving Aarthi to navigate the subsequent journey independently. As expected, 6 months of chemotherapy culminated in a clean scan. Her physical health was restored, but an emotional chasm remained, unrecorded by clinical metrics. Yet beneath that silence was a quiet resilience—a strength that carried her through each cycle of treatment with a resolve as steady as any celebrated elsewhere. The regrowth of her hair prompted a conscious decision to trim it shorter, seemingly an assertion of autonomy. Her discourse on the illness shifted to the third person, suggesting a psychological distancing. Her reactions to inquiries about the terminated engagement were guarded. She would yield only a restrained smile, which intimated a multifaceted emotional response. Her remission was certain, yet the world she stepped back into was layered with quiet hurdles—social, cultural, and unseen—barriers far more intricate than the disease itself. Survivorship Without A Map In the weeks that followed Aarthi's diagnosis, I began to notice a quiet but consistent pattern in the oncology clinic—one that extended beyond medical recovery into the unspoken social aftermath. Among young, unmarried women in India, survivorship often came with a parallel challenge of navigating shifts in how they were perceived, particularly as marriage prospects. In Indian families where marital status is closely tied to stability and future security, a woman with a cancer history, even after complete remission, somehow came to be quietly perceived as less suitable. Proposals that had once moved forward with confidence were paused or reconsidered after disclosure. In some cases, financial discussions came with requests for additional support framed as reassurance rather than rejection. These changes were seldom explicit. Yet, across time, they pointed to a deeper uncertainty—about how survivorship fits into the expectations of traditional life scripts. For women like Aarthi, the narrative shifted toward caution. There were subtle inquiries about reproductive potential or disease recurrence and private deliberations over disclosure during matrimonial discussions, even within educated circles. Meanwhile, my observation of the disparity in how survivorship was interpreted across genders in our country left a profound mark on me. A 31-year-old male investment banker who had recovered from testicular cancer was hailed in local media as a testament to fortitude. Male patients seemed to gain social capital from their cancer journeys. This suggested a cultural framework where female value was quietly reassessed, influencing their post-treatment identity through unstated societal perceptions. Digital Ghosting and the New Untouchability Within the digital landscape of curated profiles and algorithmic matchmaking, the reassessment of female survivorship acquired a new dimension. In one instance, a sustained exchange of text messages ended abruptly following the mention of cancer remission. The final message remained unanswered. This form of silent disengagement—subtle, unspoken, and devoid of confrontation—highlighted how virtual spaces can compound post-treatment vulnerability. Designed to foster connection, these platforms sometimes amplified social distance, introducing a modern form of invisibility. Similar to employment status or religion, a cancer history has become another addition to a checklist used to evaluate compatibility. When Medicine Ends, but Society Does Not Begin As a medical student, I felt a growing discomfort. Our curriculum equips us to manage treatment protocols and survival metrics but rarely prepares us for the intangible burdens that persist after cure. What captures the weight of a canceled engagement? What framework supports the quiet reconstruction of identity after remission? Aarthi's path, echoed by many others, revealed a dissonance that medicine alone could not resolve. The challenge was not solely the illness but the reality that she was now unqualified to return to her normal life. Medicine delivers clean scans and structured follow-up, but social reintegration is less defined. In that space between biological recovery and social acceptance, cancer survivors often stand at the edge of wholeness—clinically well but navigating a quieter uncertainty. A Different Ending Two years later, Aarthi's journey took a quiet turn. At a spiritual retreat in Bengaluru, she met an ear, nose, and throat resident who had lost his father to lung cancer. Their connection, shaped by shared experiences, evolved into a partnership grounded in empathy and mutual respect. They married the following year. Their invitation carried a brief but powerful line: “Cancer Survivor. Love Thriver. Come celebrate both.” Today, they comanage a private hospital in Hyderabad. Aarthi leads psycho-oncology services, whereas her partner performs surgeries. He often notes that her presence brings a calm to the clinic that no medication can replicate. Aarthi's journey continues to guide me as I progress through my medical training, reminding me that cure and closure often follow separate paths. Healing, I have come to understand, extends beyond the clinic. It often unfolds in quieter spaces where scans no longer guide us. The real curriculum in oncology lies not only in staging and response rates but in recognizing the many transitions—social, emotional, and cultural—that survivors must navigate long after treatment has concluded. Social stigma is often a second metastasis—undetectable by imaging but present in tone, hesitation, and traditions that quietly redefine survivorship. For many women of marriageable age, treatment marks not the end of struggle but the start of another kind of uncertainty. These survivors carry wounds that do not bleed. Yet, they persist, navigate, and redefine strength on their own terms. Aarthi's quiet resilience became a point of reckoning for me, not as a medical case, but as a guide. Her story is not one of illness alone, but of dignity quietly reclaimed. “Out of suffering have emerged the strongest souls; the most massive characters are seared with scars.”—Khalil Gibran. Mikkael Sekeres: Welcome back to JCO's Cancer Stories: The Art of Oncology. This ASCO podcast features intimate narratives and perspectives from authors exploring their experiences in oncology. I'm your host, Mikkael Sekeres. I'm professor of medicine and chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. In oncology, we often focus on treatment and a way to find a cure. But what about the expectations and challenges a patient may face from their diagnosis, and even discrimination, especially in different cultures? Today, we're going to examine that space with Harshil Vangipuram, a medical student from India whose JCO Global Oncology article, "Whispers After the Cure: Reflections on Marriage and Malignancy in India," touches on this complexity after treatment. Harshil, thank you for contributing to JCO Global Oncology and for joining us to discuss your article. Harshil Vangipuram: Thank you for having me, Dr. Sekeres. I was raised by a family of oncologists, my mother being a senior medical oncologist and father a senior radiation oncologist. I had exposure to contrasting worlds, which were resource constrained and a cutting edge technology world. And I have unfulfilled curiosity, and I'm still learning, forming ideals. I also see patients as my teachers, so I think that might be helpful. Mikkael Sekeres: Thank you so much for a little bit of that background. So, tell us a little bit about your journey through life so far. Where were you born and where did you do your education? Harshil Vangipuram: I was born in a state called Gujarat in the western part of India. My father got transferred to the southern part of India, so I did my education there. That's it, yeah. Mikkael Sekeres: Okay. That's enough. You're not that old. You haven't had the sort of training and final job that a lot of us have gone through. So, what about your story as a writer? How did you first get interested in writing, and how long have you been writing reflective or narrative pieces? Harshil Vangipuram: I read some books from Indian authors and from foreign, too. And they actually inspired me how patient care was being seen around globally. I always used to carry a hand note. I used to write what I used to see in the clinical postings here at AIIMS. And actually, journaling started as a stress relief for me, and slowly, after hearing patients' stories, it almost became an obligation to write about them. Mikkael Sekeres: Obligation, you use that word, which is such an interesting one. How did writing become an obligation? What did you feel obliged to do when writing about some of the patients you were seeing for the first time? Harshil Vangipuram: Many of them were having struggles which were not seen by everybody. And I got astonished by their confidence and resilience in those situations. So, I thought that I should write about them so that everybody knows about it. And these social stigmas were never talked by anyone around them. So, I felt that if I could voice them, others might eventually know about them. So, that's pretty much the reason I wrote. Mikkael Sekeres: It's so interesting. The people we meet every single day, particularly in hematology oncology, bring such fascinating backgrounds to us, and they're backgrounds that may be unfamiliar to us. And I think that as doctors and writers, we do often feel obliged to tell their stories from the mountaintops, to let other people in on some of the aspects of life and medical care that they're going through and just how inspiring some of these patients can be. Harshil Vangipuram: Yeah, yeah, very true. Very true. Mikkael Sekeres: You mentioned that your mom is a medical oncologist. What kind of influence did she have on your decision to enter medicine and perhaps your own specialty one day? Harshil Vangipuram: Observing my mother practice influenced a lot, and she taught me that medicine is not only about treating a patient, but also listening to their problems. It may be more present in the room. The textbooks I read didn't capture live experiences. I always thought that stories will stay with people longer than actual survival curves. Writing filled that gap between what I studied and what I felt in the OPD. Mikkael Sekeres: It's a great phrase you just whipped out. Patients' stories will stay with us longer than survival curves. Can you tell us a little bit about where her clinic is located? You said in southern India. Can you describe the types of patients she sees? Harshil Vangipuram: It's a small town called Nellore in Andhra Pradesh state. The patients are, most of the time, from a rural population where decisions are mostly family-driven and there's a tight community surveillance and the stigmas are more overt, too. A few of them can be from urban population also, but they have subtler discriminations towards stigmas. Mikkael Sekeres: Can you explain a little further what you mean by decisions are often family-driven? Harshil Vangipuram: If we take marriage, it is often seen as an alliance between two families that are trying to increase their social value, their economic status, and respect in the society. In arranged marriages, for suppose, it's basically driven between these concepts. Mikkael Sekeres: I don't know if it's too personal to ask, but are your parents in an arranged marriage? Harshil Vangipuram: No, not at all. Mikkael Sekeres: So not all the marriages in the clinic are arranged marriages. Harshil Vangipuram: Yeah. Mikkael Sekeres: You know, when you said that decisions are family-driven, you mentioned that people are in arranged marriages. And I wanted to talk a little bit about the stigma you highlight in your essay. I'll talk about that in a second. I thought you were going to go down a route about medical decisions being family-driven, meaning people have to support their families, and getting medical care is costly and takes time away from work, and that sometimes influences decisions about treating cancer. What examples have you seen of that in shadowing your mom? Harshil Vangipuram: I have seen patients who have Hodgkin's lymphoma, breast cancer, and ovarian cancer, who were in the age of 25 to 35, who were getting married. Many of them actually got their engagements broken. And many of them got rejected at matrimonial apps. Many of them also had been told to increase the dowry that is given actually in the form of financial security. Mikkael Sekeres: In your essay, you describe a woman who is engaged and who has a new diagnosis of Hodgkin lymphoma. Can you talk a little bit about the process of getting engaged and marrying in southern India? Harshil Vangipuram: We have the arranged marriage, love marriage, and hybrid, which is kind of arranged and kind of in love. Mostly, these problems really occur in arranged marriages. In love marriages, we don't see that that often because both are understanding about themselves and their families. And both families actually accept them both. Mikkael Sekeres: What's the process of going through an arranged marriage? What happens? Harshil Vangipuram: It can be through parents, relatives, or any known ones or through peers. We just find a man or woman who has a similar caste, who has a good financial income, and people who are respected by the society. And obviously, both the families should have aligned interests for them to accept the marriage. Mikkael Sekeres: About how often are marriages arranged and how often are they love marriages in southern India where you live? Harshil Vangipuram: Almost 90% of the marriages are arranged here. Mikkael Sekeres: Wow. So, your parents were unusual then for having a love marriage. Harshil Vangipuram: Yeah. Mikkael Sekeres: In your essay, you write, and I'm going to quote you now, "Among young, unmarried women in India, survivorship often came with a parallel challenge of navigating shifts in how they were perceived, particularly as marriage prospects. In Indian families where marital status is closely tied to stability and future security, a woman with a cancer history, even after complete remission, somehow came to be quietly perceived as less suitable." Wow, that's a really moving statement. I'm curious, what stories have you seen where, in your words, women became less suitable as a marriage prospect? Harshil Vangipuram: For women, the most important thing in a marriage is, what do you call, a family honor, fertility, and economic status in the community. So, after a long dose of chemo, many people think that people become infertile. In India, basically, we have many misconceptions and stigmas. So, people obviously think that people who have got cancer can spread it to their children or are infertile and are often excluded out of the society as a marriage prospect. Mikkael Sekeres: Gosh, that must be devastating. Harshil Vangipuram: Yeah. Mikkael Sekeres: Does the same occur for men? So, is it also true that if a man has cancer, that he is perceived as less fertile, or it may be perceived that he can pass the cancer on to children? Harshil Vangipuram: Here, after a man beats cancer, they start to celebrate it, like they have achieved something, and it's not like that for a woman. Mikkael Sekeres: In your essay, you do write about a happy ending for one woman. Can you tell us about that? Harshil Vangipuram: Yeah, a cancer survivor obviously met her true love of life in Bengaluru, who was an ENT resident then. And his father died from lung cancer. So obviously, he knew what it felt to beat cancer. Mikkael Sekeres: Yeah, he'd been through it himself. And the irony, of course, is that most cancer treatments that we give do not lead to infertility, so it's a complete misperception. Harshil Vangipuram: Yeah. Mikkael Sekeres: Tell us about your future. What are the next steps for you in your training and what do you hope to specialize in and practice? Harshil Vangipuram: Actually, I'm working on another paper which involves financial toxicity after treatment and post treatment depression. I think it would be completed in another year. And after that, after my med school is completed, I think I'm going to pursue oncology or hematology as my branch of interest. Mikkael Sekeres: Wonderful. It's thrilling to hear that somebody who is as sensitive to his patients and both their medical needs and their needs outside of medicine will be entering our field. It'll be great to know that you'll be taking care of our future patients. Harshil Vangipuram: The pleasure is all mine, sir. Mikkael Sekeres: Harshil Vangipuram, I want to thank you for choosing JCO Cancer Stories: The Art of Oncology and for submitting your great piece, "Whispers After the Cure: Reflections on Marriage and Malignancy in India" to JCO Global Oncology. To our listeners, if you've enjoyed this episode, consider sharing it with a friend or colleague or leave us a review. Your feedback and support helps us continue to have these important conversations. If you're looking for more episodes, follow our show on Apple, Spotify, or wherever you listen, and explore more from ASCO at asco.org/podcasts. Until next time, this has been Mikkael Sekeres from the Sylvester Cancer Center, University of Miami. Have a good day. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show notes:Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio:Dr Vangipuram Harshil Sai is a fourth semester medical student at All India Institute of Medical Sciences. Additional Reading Impact of Gender of the Child on Health Care–Seeking Behavior of Caregivers of Childhood Patients With Cancer: A Mixed-Methods Study | JCO Global Oncology

A Fight Bigger than Myeloma: Race Relations and Bias in Medicine

Play Episode Listen Later Oct 9, 2025 25:52

Listen to JCO's Art of Oncology article, "A Fight Bigger Than Myeloma” by Dr. Adeel Khan, an Assistant Professor of Medicine and Public Health at UT Southwestern. The article is followed by an interview with Dr. Adeel Khan and host Dr. Mikkael Sekeres. Dr. Khan shares the story of a patient whose multiple myeloma diagnosis and treatment serves as a reminder of the civil liberties progress we've made and that we have more to go. TRANSCRIPT Narrator: A Fighter Bigger Than Myeloma, by Adeel M. Khan, MD, MPH, MS I met her during the early part of my clinical training in hematology/oncology. She was in her late 70s, dressed in a rust-colored cardigan and a headwrap with patterns that reminded me of Ghanaian kente cloth. Her eyes were sharp, her tone polite but direct. You could tell from the moment she spoke that she had lived a life where she had to advocate—for herself, for her family, for her place in rooms that were not always welcoming. Her chart said “multiple myeloma, R-ISS II,” but it did not say that she had first come to an emergency room at least a year earlier complaining of back pain and fatigue and had been told it was probably arthritis or old age. It did not mention that she had seen three different doctors before someone ordered the laboratory tests that finally began to work up her anemia and increasingly compromised kidney function. It would take another trio of doctors to eventually order a magnetic resonance imaging whose ghostly lytic lesions led down the path to a bone marrow biopsy and her cancer diagnosis. When I brought this up gently during one of our early appointments, she looked at me and said, “They don't hear pain the same when it comes from someone like me.” As a Black woman from the Deep South, she had grown up learning how to navigate a health care system that did not always believe her. She told me stories about being dismissed, misdiagnosed, and interrupted. She was born into an era of structural violence where she would be ignored at best and mistreated at worst. She carried the weight of those moments, but she also carried strength, and clarity, and the kind of dignity that made people sit up straighter in their leather chairs when she entered the room. She was one of the most quietly revolutionary people I have ever known, having grown up during a time of civil rights activism. She had even taken part in bending Dr King's long arc of the moral universe toward justice and could share story upon story from her glory days. Her myeloma treatments were not easy. Chemotherapy rarely is. She shared that there were days when her body was tired of fighting, when her bones ached, her blood counts dropped, and her neuropathic pain throbbed. In the back of my mind, I thought how tragic it was that her delayed diagnosis added unnecessary complications and whether she too thought of that. She was fully mindful of the issues people with her skin color faced in our American healthcare system and society as a whole and revealed how that motivated her to carry forward. “If I don't take up space here,” she told me once, “then someone else like me won't either.” Over the course of our visits, I came to understand that she did not see her myeloma as the hardest fight of her life. Not by a long shot. Her primary struggle was centered on life in Birmingham in the 1950s where separate but equal was still the law of the land; her mother cleaned houses, her father worked odd jobs, and her own prospects were uncertain. She admired the writings of Richard Wright and Jean Toomer and was not shy in sharing her passions. One day, during a particularly tough visit—her disease had progressed and we were down to limited options—I found myself meandering. We went through the usual workup and discussions: laboratory test results, symptoms, and treatment options. I offered the prospect of clinical trials, but she shook her head gently and said, “I've done my time in experiments—I can't give myself to a system that gave my people so little.” I paused. It was the first hint of what would become a larger conversation—not just about medicine, but about history. She was well aware of the atrocities of the Tuskegee syphilis trials in her home state, the Kligman experiments on incarcerated Black men, and the forced sterilization of women of color. As dependent upon medicine as she was in her old age, it carried a bloody stain of dehumanizing racism that soured her against it. Outwardly, I had little in common with her. As a young South Asian man growing up in times more conscious of racial injustice, I was far removed from these historical crimes. Although I learned of them during my education, I did not internalize their impact on the patients in front of me in clinic. But through her I came to comprehend just how scarring and enduring these events can be and how they can rob someone of trust. And the truth is the health care system had not treated her well. She had personal stories of doctors who did not believe her pain, nurses who assumed she was uneducated, and being passed over for better options, better care, and better answers. “But I kept showing up,” she said. “Because that's what we do. We show up even when we're not wanted.” Her stories to me were revelations. In her younger years, she had helped organize teachers at her school when they tried to fire a fellow Black teacher who seemingly spoke too loud in a meeting. She had lived through redlining, through the crack epidemic, through watching young Black men vanish into prisons, and still she rose every day and worked as a public school teacher for decades. She worked for a system that largely did not work for her. I came to admire that about her—that in simply living day-to-day life with plain dignity and acute awareness of society's issues, she promoted change by living it. “You want to talk about cancer?” she once said, half laughing. “Try walking into a bank in 1972 with a good credit score and a Black face. That's a disease this country still hasn't cured.” Curiously, she did not say these things with bitterness. Not even anger, really. Just clarity. Like someone who had long ago made peace with the truth, even if it was sharp. In clinic, she challenged my every assumption—about treatment tolerance, about compliance, about who is difficult, and who is “advocating.” And she taught me to look differently at the ways bias lingers in medicine. Not just in data or policies, but in subtle moments: the tone we use when explaining options, the hesitations in our tests and referrals, and the assumptions we may not even realize we are making. And she did not just expect good care—she demanded it. She told me early on, “Don't you treat me like I'm anything other than your mother.” That landed. And in seeing patients before me now, I remind myself to wonder who they were in their past lives, what baggage burdens them, and how it all shapes their perspectives. So from my view, she fought multiple myeloma with everything she had, but from hers, she fought something bigger: an entire system shaped by inequality. And ultimately, she made me better to realize that, not just as a doctor, but as a human being. In my years since knowing her, completing my training, and beginning my practice, I reflect on her grace. I think not just about her life, but what it means to practice medicine in a world that often forgets what patients carry with them into the clinic—generations of weight, of injustice, of strength. Mikkael Sekeres: Welcome back to JCO's Cancer Stories, The Art of Oncology. This ASCO podcast features intimate narratives and perspectives from authors exploring their experiences in oncology. I'm your host, Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. I am so happy that today we are joined by Adeel Khan, who's Assistant Professor of Medicine and Public Health at UT Southwestern in Dallas to talk about his Journal of Clinical Oncology article, “A Fight Bigger than Myeloma.” Our guest's disclosures will be linked in the transcript. Adeel, thank you so much for contributing to JCO and for joining us to discuss your article. Adeel Khan: Thank you so much for having me. It's a pleasure to be here. Mikkael Sekeres: Adeel, I don't want to be disingenuous to our readers by acting as if we've just met. You and I have known each other for a decade since you were still in your training. I wonder if for our listeners you can tell us a little bit about yourself, where are you from and and walk us through your career so far. Adeel Khan: More than happy to. So, I grew up mostly in Oklahoma, but I've sort of lived around in the Northeast and here in the Southwest where I am currently. I did college at the University of Oklahoma. I did medical school at the University of Michigan. I did residency with good fortune at the Cleveland Clinic where I happened to get to know you and have continued to know you since. I did my fellowship then in hematology oncology at Beth Israel Deaconess in the Harvard system and along the way of all that I did a Masters of Public Health at Harvard and a Masters of Science and Epidemiology at Columbia, and that pinball finally settled here to UT Southwestern here in Dallas which I am very happy to make my second home. Mikkael Sekeres: That's great. I will say just for our listeners you've been a superstar since the moment you were a resident. It's been a real treat for me to get to know you over the years. Adeel Khan: Thank you so much. Mikkael Sekeres: Can you tell us a little bit about your own story as a writer? You're a good writer. We get submissions from some really good writers every single week. It's a real privilege to be an editor for the Art of Oncology section and it's always reinvigorating to me to see how many good writers there are in medicine. How did you start your journey as a writer and how long have you been writing reflective narrative pieces? Adeel Khan: I would say if I went back to let's say high school, you know, people tend to be divided into kind of like the sciency types versus the literary arts types and you're kind of an either/or, you know, you didn't really have as much crossover then. But you know, I actually didn't mind when we had an essay due and I liked writing back then, and when I entered college I did a minor in English because I actually did enjoy that and I just liked the idea of being able to put your thoughts on paper in a way immortalizing them. Adeel Khan: And then as I sort of pursuing medicine more and more, publishing is really- it has all kinds of flavors to it and scientific publishing is obviously what has been emphasized, but you know, there's so many things to talk about within medicine. There's the science and the art of the field, and as I've moved along, I've written different pieces focusing really on patient stories and interactions. And I think my motivation has always been that as I have gotten particularly nowadays increasingly busy, I've had the fortune and misfortune of becoming more and more busy, it's easy to lose the opportunity to really connect with people that makes what we do meaningful. And so in those times when you know, and they can be rare, but when you really get to connect with someone in front of you who you're helping to care for, it's really refreshing and it's rejuvenating and I've tried to keep that with me as long as I can as I've gone through my journey. Mikkael Sekeres: There's a lot of jumping off points from what you just said, Adeel. I wonder if I can start with do you consider yourself an English major who's good at science or do you consider yourself a scientist who's a good writer? Adeel Khan: I think I'm too humble to say either. I think I was really a science major who just happened to like writing and reading and kept that as a part of myself. Mikkael Sekeres: Because I think there are a cadre of doctors who are actually English majors and have learned to turn science into storytelling and that's their entrée into science and medicine. I remember I talked for a while with David Scadden about this. He's a brilliant translational scientist who's based at Mass General who also teaches a writing course to the Harvard undergrads and who was an English major when he was an undergrad at Case Western. We've talked about this, about how there are people, I'll include myself in this, who just think different, who probably have these liberal arts brains and they figured out a way to convert science into a way a liberal arts person can understand it. Adeel Khan: Yeah, I mean narrative medicine has been I think around all along and it has only kind of been recently named as a field, but I mean it very much speaks to that that there's so much more than just G proteins in medicine. Mikkael Sekeres: I'm thrilled to hear that by the way. You mentioned you were an English minor. Are there particular writers who are an influence on you or can you talk about what's the most recent book or article you've read? Adeel Khan: Oh, that is a great question. Paulo Coelho is someone I've liked for a long time, The Alchemist. I really liked it because I read it after I had lived in Egypt. I lived in Egypt between college and med school as a study abroad program, and I had actually been to the Faiyum Oasis where the protagonist in that story ends up. And so it was just a fascinating story to me that I could trace some of the steps that are discussed in the book and it's so much- it's a story about self discovery which at that phase of life that I was in was you know, very much a theme of my own life. And so that's one that definitely stands out in my head. Mikkael Sekeres: Do you think reading pieces outside of medicine makes you a better scientist? Adeel Khan: I think absolutely. I think it makes you a better human being. In some ways I lament that so much of what I do reading now is so much just about what's in the field, what's new in myeloma, what's new in hematology oncology and I sort of miss the escape to reading other things and being able to pursue it. And even broader than just what a novel really offers. I mean, I grew up reading comic books too and I've always loved superheroes and fiction whether it's Star Wars and other things. And really they're just stories and the medium- there might be connotations whether it's a comic book or a or a novel, but they're just different mediums, but the fact that they're just stories is fundamental. I actually think to myself that it's so fascinating that the earliest piece of writing that we've really retained as human beings is we believe, the Epic of Gilgamesh, which is really a story of a superhero when you think about it, you know, and it's it's fiction, it's phantasmic in so many ways. But it speaks to how stories are just vital as people. Mikkael Sekeres: And what is it about graphic novels or my kids now of course call them graphic novels. We're not allowed to call them comic books. Adeel Khan: As they've been renamed, yeah. Mikkael Sekeres: What is it about graphic novels or comic books or the story of a hero that appeals to us in medicine? Adeel Khan: I think it's in some ways a parable of what we're doing. There's something so powerful and fundamental about this idea of good-evil and we can rename it in different ways, but that you're trying to overcome something that's an issue, an obstacle. And when you think about what we do in- particularly in oncology, that's very much what we're trying to do. We're trying to overcome an illness, a disease, to try to help the person in front of us. And it has different aspects to it. It could be someone pursuing something in a lab, it can be treating someone in front of you in clinic, but that simple dichotomy of there's something good about what you're doing because there's something bad in front of you is just the fundamental that runs through it all. Mikkael Sekeres: It's fascinating. I wonder if 30, 40, 50 years ago people would have said, “Oh, it's because the doctor is the hero,” but we don't view ourselves that way anymore. The patient is the hero. I love how you posit this as a good versus evil, the evil of course being cancer and the good everything that our patients do and that we try to to help to do to overcome that. Adeel Khan: For sure. Mikkael Sekeres: You wrote a really great essay about a woman who was a patient of yours. Can you tell me a little bit about what inspired you this time to make this connection and to write about this woman? Adeel Khan: Within the past year or so as I had been just really- the fortune and misfortune of getting busier, I lamented that I just wasn't able to spend as much time with patients in the way that I used to. One of the beauties of medical school and you know, to some degree residency and certainly fellowship is that you just have a little bit more time as a trainee, student and trainee where you can really bond with your patients I think a little bit more. And so in trying to kind of refresh my motivation, I was thinking about just kind of randomly some stories that I've kept in the back of my mind and this patient's story is one that stood out to me as I was recalling things. It was so fascinating to me because she had the disease which I now focus on. And the way that she viewed it and the way that she viewed it as a part of her life was just so different than what I think most people think of. And in that way it was very revitalizing that her focus in her life was part of a broader theme of the way that I think she viewed society. And this was just one piece of her own part of that much, much larger puzzle. Mikkael Sekeres: You really write lovingly about her and about how meaningful her context was in how you cared for her and what her experience was in the medical system. I wonder if I can read a little bit of what you wrote because it really did grab me as well. I'm going to start out by quoting you where you say, “Outwardly, I had little in common with her. As a young South Asian man growing up in times more conscious of racial injustice, I was far removed from these historical crimes. Though I learned of them during my education, I did not internalize their impact on the patients in front of me in clinic. But through her, I came to comprehend just how scarring and enduring these events can be and how they can rob someone of trust.” Wow, there's a lot there. Could you start with what was your perspective as a young South Asian man growing up in Oklahoma and what your view was of racial injustice compared to what her experience was of racial injustice? Adeel Khan: Yeah, I have to admit I don't know that I thought that much of it back then and I think that that's part of what it is. You know, being someone who was South Asian, I'm Pakistani, I have Indian roots, and coming into American history and as we learned about it there's so much about slavery and the theme of slavery unfortunately and and the struggles that enslaved peoples have. And you know, as a relatively recent immigrant, I didn't see myself in that narrative. I didn't see myself in that historical reality. But I knew about it intellectually, you know, I knew about the Tuskegee Syphilis Experiments, you know, I learned about all these things and and you learned about how atrocious so much of it is. But again, not being so directly connected, I did not put myself in that same role as someone to view it so close to myself. I will say it hit a little bit more after 9/11 when you know, I was randomly stopped at airport security a little bit more often in those days and again, I think that speaks to racial injustices, you know, I was certainly profiled looking back then, I've been held by TSA in the past, but even that is very minor compared to what African Americans have dealt with here. And this patient in just kind of sharing her tidbits during our time together, I was not directly asking her so much of this. She was really offering a lot of it to me as we would talk and she would be very generous in sharing parts of her story. And over time I kind of understood the broader narrative of her life. You know, it was clear how much of all that was actually in the forefront of her head. Adeel Khan: And I think she might have been a little bit more unique in the way that she kept it there, but she was hyper vigilant of issues of society and the roots that brought a given society to where it is here. I kind of got to know her, this is during the COVID pandemic and this was after the injustice of what happened to George Floyd and so it was a theme that I think people were talking about more and so I think she felt comfortable in saying really what was quite a bit that was stewing in the back of her head seemingly at all times. Mikkael Sekeres: It's so interesting you talk about what you endured after 9/11 as being, I'm going to quote you now, “minor” compared to what she's been through, but even a minor affront like that can really compromise your trust. You write about her, “As a Black woman from the deep South, she had grown up learning how to navigate a healthcare system that did not always believe her.” Can you expand on that a little bit? How is it that the healthcare system didn't believe her and what can we do going into interactions with patients from different backgrounds where we're incorporating that there's a compromise of trust and we have to make up for that? Adeel Khan: Yeah, and I think you know, it's so unfortunate that so many people have stories like this where, in her case really it was back pain that was her presenting symptom. This is long before she knew me. And she'd had the back pain for quite some time, but being an older woman, she was in her 70s at that time, she was not in phenomenal health for other reasons. It sounds like she was just kind of ignored, told that it was old age, tendon changes, she did not have meaningful imaging for some time. When she finally did after seeing a slew of different providers, that's when it was revealed like there's something more significant here. And then when you kind of piece that a little bit retrospectively and I think she certainly sensed this and I did when I- hindsight's always 20/20, when I looked through things, it's like, well, this probably could have been caught much earlier. It's just that no one really I think listened to what she was speaking to with her pain and the gravity that was actually behind it. And it just speaks to the fact that I think we have to be more thoughtful in what we take away from patients and not to ignore even small comments because they might be revealing of something much bigger behind them. Mikkael Sekeres: You quote her, you have some really great quotes in your essay where you just listen to what she says and transcribe it because what she says is very meaningful. And one of the quotes you provide from her is, “They don't hear pain the same when it comes from someone like me.” Wow. “When it comes from someone like me,” someone like her, how was it that people weren't hearing her description of pain, something that was different that was going on in her body and how can we be more attentive to people when they complain about things like pain? Adeel Khan: It's unfortunate that there's even known data to show how depending upon a patient's melanin content in their skin, how likely they are to get pain medications and what happens to them is different and this is an unfortunate example of that where I think she just wasn't heard properly. And so it wasn't addressed properly and she was not shy about saying that. I mean I think she sensed that. She was very clear in feeling that herself and in wanting to have better care, she was still prevented and hence why she had to go from provider to provider. Mikkael Sekeres: You've lived in a bunch of different places in the country. I mean, following your path, you've been in Oklahoma, you've been in Michigan, Ohio, Massachusetts, and now Texas. Do you think that we as providers have to have different levels of sensitivity depending on where in the country we're practicing and how some of our patients' trust in healthcare may have been compromised in those different parts of the country? Adeel Khan: I think absolutely. I mean this particular patient was from Alabama which has a heavy history that she was again very aware of and for those of us reading history books are also very aware of too. And it's interesting how, while the U.S. is in some ways- has some aspects that are monolithic, but it's very much not so. It's very patchy and people are different, you know, if I take one theme that we're talking about here is obviously racial injustice, but if you take something like obesity, you know, prevalence rates are very different throughout the country and attitudes surrounding it are also very different. And I think we do- ought to be mindful that in treating the patient in front of us, it's not done without context. And so how they view their illness and their situation is going to be different depending upon the state, depending upon the city, depending upon actually even the era that they grew up in. So I would say now, if you took actually a similar patient, but you put her in a very modern context post-year 2000, she's likely to have different feelings of the situation around her than someone who was born in this case in the 1940s. And that just speaks to the fact that circumstances change and we should be recognizing that as providers, even though it's not always easy to. Mikkael Sekeres: Well, it just emphasizes how very important it is to know the history of the place where we practice and how it's affected our patients' perceptions of healthcare and trust and being cared for, particularly now as there's such a movement to whitewash that history and eliminate it from major institutions like the Smithsonian. It has been such a pleasure to have Adeel Khan here. He is Assistant Professor of Medicine, Public Health at UT Southwestern in Dallas and wrote just a great JCO article called “A Fight Bigger Than Myeloma.” Adeel, thank you so much for submitting your article and for joining us today. Dr. Adeel Khan: Thank you so much for having me. It's been a pleasure. Mikkael Sekeres: If you've enjoyed this episode, consider sharing it with a friend or colleague or leave us a review. Your feedback and support helps us continue to have these important conversations. If you're looking for more episodes and context, follow our show on Apple, Spotify, or wherever you listen and explore more from ASCO at ASCO.org/podcasts. Until next time, this has been Mikkael Sekeres for JCO Cancer Stories: The Art of Oncology. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show Notes Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr Adeel Khan is an Assistant Professor of Medicine and Public Health at UT Southwestern.

Income Among Adolescents and Young Adults Surviving Cancer

Play Episode Listen Later Oct 9, 2025 16:16

Host Dr. Shannon Westin and guest Dr. Giancarlo Di Guiseppe discuss the JCO article "Long-Term Dynamic Financial Impacts Among Adolescents and Young Adults With Cancer: A Longitudinal Matched-Cohort Study" TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Shannon Westin: Hi everybody and welcome to another episode of JCO After Hours, the podcast where we go in depth on manuscripts that are published in the Journal of Clinical Oncology. I'm your host, Dr. Shannon Westin, social media editor of JCO and gynecologic oncologist extraordinaire. I'm so very excited to talk to you today. We're going to speak about "Long-Term Dynamic Financial Impacts Among Adolescents and Young Adults With Cancer: A Longitudinal Matched-Cohort Study." And I'm joined today by Dr. Giancarlo Di Giuseppe. He has a PhD in epidemiology that he actually just defended with this very work you're going to hear about today at the Dalla Lana School of Public Health at the University of Toronto. He is now a research fellow at the Hospital for Sick Children. Welcome, Dr. Di Giuseppe. It's so exciting to have you. Dr. Di Giuseppe: Thank you so much for having me. Dr. Shannon Westin: So we'll get right to it. Let's level set. Can you talk a little bit about the financial impact of cancer on survivors in general? I think this has been a growing area of interest and research, certainly. Dr. Di Giuseppe: Yeah, and I think that's a very important question, and I'm so happy that this research is now becoming more popular in the research world because it really addresses a critical issue that cancer survivors and their families must face. You know, you're diagnosed with cancer, and now you need to take time off work because you're hospitalized for chemotherapy. You're going back and forth to the hospital, and that all requires time away from your employment, and as a result of that, that has a significant financial strain, both on you and your family. And that's during therapy. Now, in survivorship, in the years after you've survived your cancer, you still need to deal with all the late effects associated with your treatment and your disease, and that can be psychological, physical, and that impacts your workability as well. So, it's not just exclusive to individuals undergoing treatment but also in survivorship afterwards. It really gets the financial strait that you face as a cancer survivor because you're time away from work and your lost productivity. Dr. Shannon Westin: Yeah, that makes sense. Then I think it would be great to talk a little bit specifically about the patient population that you studied in this particular manuscript. Can you talk a little bit about the adolescent young adult cohort, you know, why you singled out this particular group of people? Dr. Di Giuseppe: Absolutely. Adolescents and young adults, or AYAs, which I'll now refer to them as - I'm one of them - we're at a unique crossroads of our life and in our developmental stage of life. We are finishing our post-secondary education. We're entering the workforce. We're forming romantic relationships, and we're really achieving financial autonomy. It's because of this unique developmental stage in life where we've become quite susceptible to health shocks such as cancer. Really, does a cancer and the associated negative financial impacts affect our long term trajectory? So, I'm just finishing my PhD. If I was diagnosed with cancer, I would require a year or two away from my studies. I may or may not finish my education that could then impact my employment and then my financial outcomes later on in life. So it's really this unique population who are going through so many transitions and changes in their lives. How does that cancer really impact that life course trajectory? I think it's unique from an adult who might have, you know, large savings where they can bear the brunt of their cancer financial impacts, whereas AYAs may not have that same financial stability, provide a safety net for the financial impact resulting from their disease. Dr. Shannon Westin: You broke my heart a little bit. I realized I'm no longer in that group, so I guess it's time to move on. Okay. So, let's talk a little bit about the overall design of the study. Can you just kind of walk us through how you set everything up? Dr. Di Giuseppe: Yeah, absolutely. So it's a matched cohort study at the population level here in Canada. We have large national administrative databases, and we have this really unique set of data at the national level through Statistics Canada that we can link our cancer registry to tax records. It really provides this unique opportunity to longitudinally follow individuals from their disease forward in time. The main overall design is the matched cohort study. At the time of diagnosis of a cancer case, they're matched to someone from the population on certain characteristics. I follow these individuals from the index date of their cancer case forward in time. The crux of the study itself is a quasi-experimental two-group pre-post study design where I have information before the cancer diagnosis, I have information from their income after their cancer diagnosis, and it's really quantifying how much does that total income change from before the cancer to the after-cancer period. Dr. Shannon Westin: I'm always intrigued about hearing more about financial toxicity in general, certainly very multi-dimensional. Can you speak a little bit about the different ways that you can assess this and measure this and kind of what you chose? Dr. Di Giuseppe: Yeah, so financial toxicity really has two main spheres of measurement. There's a direct and the indirect measurements of financial toxicity. So your direct financial toxicities could be related to actually paying for medical treatment and any sort of financial burden as a direct consequence of your disease. Fortunately here in Canada, we have a universal health care system, so patients don't have to pay directly for most of their treatment. There's also indirect financial toxicities, which are not a direct result of the disease. So in this study here, one of the, or the indirect financial toxicity that I measured was the financial impact to income. That's not the only indirect financial toxicity. There could be out-of-pocket expenses for drugs that may not be covered in the universal health care system here. It could be lost productivity at work. There's really this direct and indirect financial toxicities that together result in a significant financial burden and hardships for cancer patients and survivors. Dr. Shannon Westin: Okay, so you guys did a lot of matching. It was extensive. Can you speak a little bit about the factors you used to match your patients and your controls and kind of why you chose them? Dr. Di Giuseppe: Yeah, absolutely. The matching I think is a really critical aspect of the study, and it really establishes this baseline period of individuals who are cancer-free, who look as similar as possible to the individuals who would eventually develop cancer. So I matched on birth year, sex, marital status, whether or not they had children, if they were born here in Canada or not, as well as a geographic measurement of census division. So it's really in the city or in a rural town. Then I also matched on a 5% buffer of their total income in the year prior to the cancer diagnosis. All this matching was really done in the year before they were diagnosed, and it's to establish this comparator cohort of individuals from the general population who looked as similar as possible to the individuals, or the AYAs, who would develop cancer. It's again to establish this baseline period of a control cohort who looks as similar as possible. So any differences that we might see after the cancer can be attributed to the effects of the AYA who would develop cancer. It's quite powerful, I think, from a study design perspective because it establishes causal inference methods through the study design and through the matching itself. Fortunately, I was able to match on an extensive list of covariates given the large population-based data that I used, particularly the tax records. Tax records contain a whole wealth of information, your marital status, your sex, your income, where you live. So it really provided this rich opportunity to match as closely as possible the AYAs who would develop cancer to someone from the population who wouldn't. Dr. Shannon Westin: Yeah, and I mean I think that's the only way to do this type of research and really make it generalizable and actually, you know, know that you can trust the results that you've got. So I just want to again congratulate you because I think this was just- when I read the design, I was so impressed. So now that we know the design and we understand everything, let's talk a little bit about the characteristics of the actual patient population that you studied. Dr. Di Giuseppe: Yeah, for sure. So average age of diagnosis was in their early 30s, so around 32 years old. The breakdown of the population was mostly females, so I think two-thirds of the cohort were actually females who were diagnosed with cancer. Really, a lot of the cancers were thyroid and the breast cancers. These cancers are more common in women than they are in men. So it's really reflective of the different distribution of cancer in AYAs compared to other populations like in children or in older adults. Dr. Shannon Westin: All right, bottom line. What did your primary analysis demonstrate and how was the income different based on the types of cancer that people might have been diagnosed with? Dr. Di Giuseppe: Yeah, the bottom line is actually quite a disturbing message, I would say, and it's really that cancer causes this long, prolonged financial hardship in survivors. That's, I think, a very important result from the study, and I think it has far-reaching implications. This study demonstrates that these individuals who were diagnosed with this disease that is unforeseen also pay a financial price, and that sustains for many years after their diagnosis. That's overall on average. Once I dove deeper, actually looking at the different cancer types, the message actually gets even more disturbing, I would say, particularly in some disease subgroups. So the central nervous system cancer survivors really have a large reduction in their income, which sustains over 25%, 10 years after their diagnosis, and they never really recover financially from their disease. There are some groups of cancer survivors who really pay a large financial price for their disease. Dr. Shannon Westin: I don't know if you're able to tease this out. This is just me thinking off the top of my head. Do you think it's the long-lasting side effects? Dr. Di Giuseppe: I think you hit the nail on the head there, absolutely. I think what we're seeing here is a direct result of the late effects that cancer survivors experience. CNS cancer survivors, whether that is a surgical resection, radiation to the head for their tumor, the late effects really impact these individuals in the post-cancer survivorship period. So I think what we're really seeing are these late effects here. Dr. Shannon Westin: The other thing I was kind of struck by is the differential and income loss over time. Can you speak a little bit about that in your work? Dr. Di Giuseppe: Yeah, absolutely. There really is this period of financial vulnerability in the first couple years of diagnosis. So that's year zero, one, two, and three, these first couple years when these individuals are diagnosed with cancer, they are significantly impacted by their disease financially. Some of these reductions in their income is 15%, 20% in the year of diagnosis and the year afterwards. It's unsurprising because this is when these individuals typically are undergoing their treatment. They're not working. They may have even lost their job or quit their job. So it's really reflective in the results in that first few years of their diagnoses where these financial impacts are the largest. I think it provides an opportunity where certain interventions might alleviate some of these large reductions in their income. Dr. Shannon Westin: Well, I really was disturbed by your work, and I hate to kind of say it that way because it's such important work. So I'm really- congratulations on everything that you're able to achieve and especially your PhD. But I think shining a light on these types of things is always pretty rough when you really look at the nitty-gritty details. So any thoughts about where we go from here, how do we support these people? Dr. Di Giuseppe: I think we can support them at multiple different levels. So at the individual level, I think within the clinic setting, financial screening for financial toxicity, financial literacy, I think all these things can be incorporated into cancer care continuum to kind of educate AYAs with cancer about the financial implications of their disease, both in the short and the long term. So I think educating these cancer patients is important. I think at the employer level, really working at the institutional level to incorporate workplace accommodations that might facilitate the return to work process for cancer survivors after their treatment or during, I think would also make the financial burden slightly less if cancer survivors are able to return to work or not have to quit their job because of their disease. And then return to work easier, I think might alleviate some of the employment consequences that these individuals face, which then lead to their adverse financial effects. Then I think also at the policy level, at the governmental level, whether that's incorporating any sort of fiscal stimulus for cancer survivors, whether they're under treatment or in survivorship, any sort of tax breaks that they might be available to them to kind of alleviate some of that financial stress. The reality of it is being diagnosed with cancer and having your income reduced by even 5% - cost of living is expensive, especially now - so I can't even imagine what cancer survivors who are in this economy are facing with rising inflation and cost of living going up. So I think really having tax breaks as well as financial aid for these cancer survivors could really support them both in their cancer journey while they're undergoing treatment as well as some of the sustained effects that they experience afterwards. It's particularly important, as we touched on earlier, for CNS cancer survivors, right? These individuals have this sustained effect that never really returns back to normal, and I think having sort of disability pension or kind of financial aid for these individuals to support them, I think is important. Dr. Shannon Westin: We see this all the time in gynecologic cancers, these young women that support their families, young children, and then lose their ability to do so due to their diagnosis and the treatment they have to receive. So I can't say this enough how important this work was and how honored I am to get to speak with you today. I learned a ton. And thank you to all of you listeners. We're just so excited to have you. This has been long term dynamic financial impacts among adolescents and young adults with cancer: a longitudinal matched cohort study. Thanks again for listening to JCO After Hours, and please do check out our other offerings wherever you get your podcasts. Have an awesome day. 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.

JCO Article Insights: Phase I DLL3/CD3 T-Cell Engager in DLL3-Positive SCLC or NECs

Play Episode Listen Later Sep 29, 2025 12:51

In this JCO Article Insights episode, Dr. Ece Cal interviews Dr. Martin Wermke, author of the JCO article, "Phase I Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas." TRANSCRIPT The disclosures for guests on this podcast can be found in the transcript. Dr. Ece Cali: Welcome to this episode of JCO Article Insights. This is Dr. Ece Cali, JCO editorial fellow, and today I am joined by Dr. Martin Wermke, Professor for Experimental Cancer Therapy at Dresden University of Technology, to discuss the manuscript “Phase 1 Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-like T-Cell Engager Obrixtamig in Patients with DLL3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas.” Obrixtamig is a bispecific T-cell engager that binds to DLL3 on tumor cells and CD3 on T-cells. This manuscript presents the phase 1A dose escalation results of Obrixtamig in patients with DLL3+ small cell lung cancer and neuroendocrine carcinomas. In this study, 168 patients were treated with Obrixtamig across four different dosing regimens. 49% of the patients had small cell lung cancer, 42% had extrapulmonary neuroendocrine carcinoma, and 8% had large cell neuroendocrine carcinoma of the lung. Patients received a median of two prior lines of therapy. 33% of the patients had brain metastases at baseline. Of note, this trial did not mandate baseline brain imaging. Maximum tolerated dose was not reached. 88% of the patients experienced a treatment-related adverse event, however, only 3.6% of the patients had to discontinue treatment due to treatment-related AEs, and dose reduction due to treatment-related AEs was documented in 2.4% of the patient population. Similar to the other DLL3-targeted bi-therapies, the most common adverse events included CRS in 57%, dysgeusia in 23%, and pyrexia in 21% of the patients. CRS events were mostly mild. They occurred more frequently in the first two to three doses. 9% of the patients experienced ICANS, of which 3% were graded as Grade 3 or higher. And let's review the efficacy results. Responses were only seen in patients who received 90 microgram per kg or more once weekly or once every three weeks dosing. The objective response rate in patients who received an effective dose was 28%. If we review by tumor type, 21% of the small cell lung cancer patients, 27% of the extrapulmonary neuroendocrine carcinoma patients, and 70% of the large cell neuroendocrine carcinoma patients had objective response. Median duration of response was 8.5 months, though this data is immature due to short follow-up. Dr. Wermke, DLL3-targeted bispecific T-cell engagers are reshaping the treatment landscape of small cell lung cancer. This trial investigates Obrixtamig in other high-grade neuroendocrine tumors as well. Can you put this trial into context for us and explain why it may represent an important step forward? Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to discuss our data today. I think the data with Obrixtamig in small cell lung cancer are largely similar to what has been observed with other bispecific T-cell engagers such as tarlatamab with respect to the response rate and duration. It has, however, been to be mentioned that BI 1438001 had a bit more liberal inclusion criteria than other trials around. You already mentioned the fact that we allowed the inclusion of patients without mandatory brain imaging, which led to some patients having their brain mets been diagnosed during the treatment with obrixtamig and then adding to the progressive disease patients. That is something which was not the case with the tarlatamab trials where you really had to have a brain imaging before, and in the Phase 1 trial you were even required to treat the brain mets before you included the patient. So it is a bit different, more poorest patient population. I think the trial adds on existing data by being the first trial to also include non-SCLC neuroendocrine carcinoma of other origin, for example from the gastrointestinal tract, and also by including large cell neuroendocrine carcinoma of the lung, which is a really hard to treat pulmonary neoplasm which currently lacks any standardized treatment. So that is really a step forward which we will build on in the future. Dr. Ece Cali: And one thing I would note in this trial, only patients with tumor expressing DLL3 were enrolled. Can you tell us a little bit more about this target, DLL3 in the context of neuroendocrine tumors, and does DLL3 expression predict clinical outcomes after treatment with DLL3 BiTEs, or do we actually need other predictive biomarkers for these novel agents? Dr. Martin Wermke: Yeah, thank you. That's a pretty interesting question. First of all, DLL3 is an atypical notch ligand, which is expressed by the majority of neuroendocrine carcinomas, virtually absent on healthy adult tissues. Therefore, turning it really into a bona fide target for T-cell engaging therapies, pretty low risk for on-target off-tumor side effects. We found that in all the patients we screened, we had an expression rate of about 94% in small cell lung cancer, 80% of large cell neuroendocrine carcinoma of the lung were positive, and also about 80% of the extrapulmonary neuroendocrine carcinoma. So it's really a high prevalence. So the fact that we only included DLL3+ tumors still means we included most of the patients that presented with these diseases. I think at the moment there are no data suggesting a clear-cut association between DLL3 expression levels and outcome on DLL3 CD3 T-cell engagers. There's also not a lot published. If you want to find this out for tarlatamab, you have to look into their patent to really see the data, but it's not clear-cut and I'm sure we need other markers to complement that. And I think what probably plays a major role is intrinsic T-cell fitness. So the question how really diseased your T-cells are, how old you are, because age also correlates with the fitness of the immune system, and other patient characteristics such as tumor burden, we've seen all across the board that the higher the tumor burden, the lower the rate of prolonged response is in such trials. And I also think we need to focus on other components of the tumor microenvironment. So see how high the T-cell infiltration with obrixtamig is and how abundant suppressive elements like regulatory T-cells or myeloid-derived suppressive cells are. That is work which is currently being done. Data are emerging, but I don't think that at the moment we have any clear biomarker helping us to select who should not receive DLL3 T-cell engagers. Dr. Ece Cali: Those are great points and there is a lot we need to learn about how to use these novel agents in the future. I'd like to highlight the results in large cell neuroendocrine carcinoma of the lung. The response rate in this group was remarkably high at 70%. Though we should note the small sample size of only 14 patients in this trial. After first line chemoimmunotherapy, current approved options for this population have very modest clinical activity. Given these trial results, how do you envision the field moving forward for patients with large cell neuroendocrine carcinoma? Dr. Martin Wermke: Yeah, I think LCNEC is really an area which urgently needs further improvement of therapeutic standards. At the moment, as I said, there is no real standard. We are usually extrapolating from results we have in small cell lung cancer or non-small cell lung cancer, but I don't think we have too many prospective trials really informing this. Of course, 14 patients is a small sample size, but I think it's still fair to say that we can claim that DLL3 T-cell engagers are not doing worse in LCNEC than they do in SCLC. And that's why I think we really need to move forward clinical trials that are specifically targeting this population. Although I fear a bit that, given the rareness of this disease and the aggressiveness of its phenotype, that this is probably not the main focus of the pharmaceutical industry. So I think it's up to us academic investigators to really come up with investigator-initiated trials trying to fill the knowledge gaps we have here. Dr. Ece Cali: And one more thing that I want to talk about is the accessibility for these drugs. These novel agents are showing real promise in improving outcomes for patients with high-grade neuroendocrine tumors, an area where progress has been limited until very recently. However, as DLL3 BiTEs become more widely used, issues of logistics and access come into sharper focus. With unique toxicities and the specialized monitoring, their use is restricted to certain centers. Looking ahead, what kinds of strategies could help mitigate some of these adverse events or make these treatments more broadly available? Dr. Martin Wermke: Yeah, I think if you look at countries like the United States where tarlatamab has already been approved, we can see how the management strategies are evolving. I've heard about a colleague equipping their patients with thermometers and a pill of Dexamethasone, alongside with a temperature control protocol and clearly instructing them, "If you measure a temperature above a certain level then start taking the Dexamethasone and come back to our office and we're going to take care of you." I think that's one way to move forward. I think we are lucky in a way that CRS usually manifests within the first 24 hours. This was the same in our study, like in the tarlatamab studies. So we really know when the time of trouble is for our patients. And in this time, I think we need to instruct the patients to stay close to the hospital. I don't think we need to hospitalize all of them, but we probably need them to stay in a nearby hotel to be able to reach the emergency room if needed in a short period of time. And I think we can also learn in this strategy how to manage bispecific antibodies from the experience our colleagues in hematology had because they have been using bispecific T-cell engagers for quite some years right now and they developed strategies and networks that were able to successfully treat these patients also on an outpatient basis. And I think that is clearly an experience we need to follow, acknowledging that we are talking about diseases which are much more frequent than the standard hematology indications. Dr. Ece Cali: Thank you so much, Dr. Wermke, for this informative discussion and for sharing your perspective on this evolving field. Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to talk about data. It was really great being able to share that, and I really think that we are just at the beginning of a new exciting area for the treatment of neuroendocrine carcinomas, and I think much improvement is yet to come for our patients. Dr. Ece Cali: Yes, that's really exciting. And thank you everyone for listening to JCO Article Insights. Please come back for more interviews and article summaries and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on this 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. Martin Wermke's Disclosures Honoraria: Lilly, Boehringer Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis, Pfizer, BMS GmbH & Co. KG, Regeneron, MJH/PER, Takeda Consulting or Advisory Role: Bristol-Myers Squib, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, immatics, Bayer, ImCheck therapeutics, AstraZeneca, Tacalyx, Regeneron, Daiichi Sankyo Europe GmbH, Zymeworks, PharmaMar, Iovance Biotherapeutics, T-Knife, Genentech Research Funding: Roche Patents, Royalties, Other Intellectual Property Travel, Accommodations, Expenses: Pfizer, Bristol-Myers Squibb, AstraZeneca, Amgen, GEMoaB, Sanofi/Aventis, immatics, Merck Serono, Janssen Oncology, Iovance Biotherapeutics, Daiichi Sankyo Europe GmbH"

SC Pembro, Biotin, P5-yr POLARIX data

Play Episode Listen Later Sep 25, 2025 18:00

The long awaited subcutaneous formulation of pembrolizumab is not FDA-approved. We discuss its administration and toxicity & PK differences vs. IV use. Biotin supplementation can interfere with lots of labs cancer patients get routinely - Who knew? (Ahem, not me.) Link: https://doi.org/10.1200/OP-25-00693 POLARIX 5-year Data: https://doi.org/10.1200/JCO-25-00925

data fda iv pk ahem biotin jco

Episode 65. Circulating Tumor DNA in DLBCL with Dr. Ash Alizadeh and Dr. David Russler-Germain

Medscape InDiscussion: Multiple Myeloma

Play Episode Listen Later Sep 24, 2025 53:08

In this episode of Blood Cancer Talks, hosts Eddie, Ashwin, and Raj welcome two distinguished experts to explore the cutting-edge field of circulating tumor DNA (ctDNA) in B-cell lymphomas. Dr. David Russler-Germain, a lymphoma clinician from Siteman Cancer Centre at Washington University in St. Louis, returns as a familiar voice to the podcast audience. Joining him is Dr. Ash Alizadeh, the Moghadam Family Professor of Medicine, Oncology, and Hematology at Stanford University and leader of the Cancer Genomics Program at Stanford Cancer Institute. Dr. Alizadeh has been instrumental in advancing our understanding of lymphomagenesis and lymphoma genetics over the past two decades, pioneering multiple ctDNA techniques that are revolutionizing cancer care. Together, they discuss the transformative potential of ctDNA technology in B-cell lymphomas, particularly DLBCL, covering everything from the technical evolution of biomarker detection to groundbreaking clinical data that may reshape how we monitor and treat these aggressive cancers. Key Discussion Topics1. Genetic Heterogeneity in B-Cell LymphomasComplex genetic landscape of DLBCLImplications for treatment strategiesNeed for personalized approaches 2. Clinical Need for ctDNA in LymphomaWhy ctDNA is needed in aggressive lymphomas:Curative vs. non-curative treatment settingsLimitations of current PET imagingAdditional prognostic information beyond imagingRisk stratification capabilitiesPotential to avoid overtreatmentTherapy adaptation opportunities 3. Challenges in Lymphoma MRD AssessmentWhy lymphoma MRD is more complex than other hematologic malignancies:Differences from acute leukemias, CLL, and myelomaTechnical challenges specific to lymphoid tumorsLower circulating tumor burden compared to liquid tumors 4. ClonoSEQ TechnologyMechanism: Immunoglobulin sequencing approachAdvantages: Established platform with regulatory approvalDisadvantages: Limited sensitivity in peripheral blood, requires adequate tumor sample 5. CAPP-Seq TechnologyFull Name: Cancer Personalized Profiling by Deep SequencingInnovation: Developed ~10 years ago by Dr. Alizadeh's groupMechanism: Targeted sequencing of cancer-specific mutationsAdvantages: High sensitivity, personalized approach 6. PhasED-Seq TechnologyEvolution: Next-generation advancement of CAPP-SeqKey Improvements: Enhanced sensitivity and specificityTechnical Advances: Phased variant detection Clinical Data Highlights1. Remission Assessment by ctDNA in LBCL on 5 prospective studies of frontline anthracycline-based chemo-immunotherapy: https://pubmed.ncbi.nlm.nih.gov/40802906/2. Prospective validation of end of treatment ctDNA-MRD by PhasED-Seq in DLBCL patients from HOVON-902 clinical trial: https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.70003. Korean data on prognostic utility of ctDNA: https://ashpublications.org/blood/article/142/Supplement%201/69/501573

S2 Episode 3: When Is the Best Time to Use CAR T-Cell Therapy in Multiple Myeloma?

Play Episode Listen Later Sep 23, 2025 24:38

Joseph Mikhael, MD, and Krina K. Patel, MD, MSc, discuss considerations for CAR T-Cell therapy in multiple myeloma, including age, access, and bridging therapy. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002715. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma https://emedicine.medscape.com/article/204369-overview CARTITUDE-1 Final Results: Phase 1b/2 Study of Ciltacabtagene Autoleucel in Heavily Pretreated Patients With Relapsed/Refractory Multiple Myeloma https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8009 Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/37272512/ Plain Language Summary of the KarMMa-3 Study of Ide-cel or Standard of Care Regimens in People With Relapsed or Refractory Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/38651976/ CAR T-Cell Therapy Toxicity https://www.ncbi.nlm.nih.gov/books/NBK592426/ Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience https://pubmed.ncbi.nlm.nih.gov/28205024/ Incidence and Outcomes of Cytomegalovirus Reactivation After Chimeric Antigen Receptor T-Cell Therapy https://pubmed.ncbi.nlm.nih.gov/38838226/ Long-Acting Granulocyte Colony-Stimulating Factor in Primary Prophylaxis of Early Infection in Patients With Newly Diagnosed Multiple Myeloma https://pubmed.ncbi.nlm.nih.gov/35064823/ Revisiting the Role of Alkylating Agents in Multiple Myeloma: Up-to-Date Evidence and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/37244325/ Bispecific Antibodies for the Treatment of Relapsed/Refractory Multiple Myeloma: Updates and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/38660139/ FDA Eliminates REMS for Approved CAR T-Cell Therapies https://www.aabb.org/news-resources/news/article/2025/06/30/fda-eliminates-rems-for-approved-car-t-cell-therapies

action study md treatments relevant outcomes patel msc best time ide incidence multiple myeloma medscape car t cell therapy clinical experience car t cell jco

Postmastectomy Radiation Therapy: ASTRO-ASCO-SSO Guideline

ASCO Guidelines Podcast Series

Play Episode Listen Later Sep 16, 2025 15:38

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.

Brown Paper Bags: Beware of Patients Bearing Gifts

Play Episode Listen Later Sep 12, 2025 30:50

Listen to ASCO's Journal of Clinical Oncology Art of Oncology article, "Brown Paper Bags” by Dr. Stephanie Graff, who is an Associate Professor of Medicine at Brown University and Director of Breast Oncology at Brown University Health in Providence Rhode Island. The article is followed by an interview with Graff and host Dr. Mikkael Sekeres. Dr Graff shares how she handled receiving a gift from a patient. TRANSCRIPT Narrator: Brown Paper Bags, by Stephanie Graff, MD, FACP, FASCO Minor demographic features of the patients described have been altered to honor their privacy “Why are you being weird about opening the bag?” he asks. The gift that William brought me is still sitting on the edge of the clinic examination room counter, the proverbial elephant in the room. He presented it to me the moment I entered the examination room, excited as a child giving their first Christmas gift. I have demurred, stating I will open it later. I have tried to avoid opening the bag, explaining that I do not like opening gifts in front of people. William is as tenacious about me opening this gift right now as he is about facing his disease. I treat William for male breast cancer. I have always called him William because it is what the electronic medical record says as his preferred name. It is his first name, and when I verified on our first meeting what he preferred to be called, he said “William is fine,” but just like the Sheryl Crow song says, “I'm sure it's Bill or Billy or Mack or Buddy.” 1 William is electric. He lights up the examination room, engages my staff while playfully ribbing them, and has a laugh that reverberates down the hallway. He comes to each visit with a colorful story about the events that have transpired since our last appointment, vividly painting images of his children and grandchildren and his life outside the clinic walls. He swells with pride discussing his grown children like a new mother showing off photos of her baby. “Ryan just finished the most beautiful presentation deck for work. You should see it. Those slides! I bet he would show it to you.” Ryan works in banking or finance or insurance—I cannot remember—but I confess I never took William up on the offer to see the slide deck. Abruptly, William stands up, moving faster than an elderly patient with metastatic cancer should be able to move. In a single swift movement, he grabs the brown paper bag from where I abandoned it on the counter and drops it in my lap. “Open it!” I sigh deeply, carefully unroll the top, and peek in. “I got those for the mister!” he exclaims. Inside is a bag of Werther's hard caramels. As relief floods me, I laugh a deep, slow laugh of appreciation for this 70-something man and his ability to brighten the world around him in the most surprising ways. During our last clinic visit, he told me hard caramels take the chemotaste out of his mouth, and I had confessed that my husband is also Werther's devotee, but prefers the soft chews. William made a case then and there for the hard caramels and told me I should try to get “Mr Dr Graff” to make the change. He approached the soft caramel versus hard caramel discussion with the intensity of a high school debate champion. Needless to say, the Graff household now alternates our caramels—enjoying both hard caramels and soft chews. “Seriously. What gives with you and the bag?” he probes again. I recognize that William is not going to let this go. He is too astute and persistent. So, I decided to tell him the whole truth about gifts from patients and brown paper bagsThat first year as an oncology fellow, after months on inpatient consults, I finally started outpatient clinics just as the holidays season began. The patients, many of whom had deep and long relationships with the attending oncologists—the same relationships I was eager to build, the relationships that drove me to oncology as a profession—brought in gift after gift, homemade cookies, handmade quilts, and jars of homemade jam. It was rarely something elaborate as the patients knew the faculty could not accept anything too over the top, but it often showed the same tender thoughtfulness that you show a dear friend or favorite relative. Their favorite coffee. A T-shirt of a favorite band. Or something jovial, like a rival sports team or college's coffee mug. It was during this time of the busy holidays, maybe the second week of December, in my own fellow's clinic, that one of my patients with solid tumor arrived with a small brown paper bag. He of course had synchronous primary malignancies that in no way aligned for a simple plan of care and was experiencing dreadful side effects, which seemed to be the way of fellow's clinic. I had been seeing him quite often, pouring every ounce of my nascent skills into trying to help him through his treatment. He handed me the bag, and in my enthusiasm and naivety and holiday spirit, I bubbled with excitement thinking “oh, he brought me a little gift!” But my own thoughts were pouring over him saying “I brought this in for you because…” and as he was saying the rest, I tore open the bag, all the while with my eyes on him as he spoke, and plunged my hand into the bag, grabbing the…what exactly…cloth something…to hear him saying…. “…because I wanted you to see how bad this diarrhea is! Pure liquid. Bloody. Constant. I can't even make it to the bathroom,” he was saying. Yes. I was holding—in my bare hand—his soiled, blood-stained underwear. Merry Christmas. I have not excitedly torn open a mystery gift or plunged my hand into a bag since. This is not a lesson that took more than one time to learn. In retrospect, perhaps my patient did give me a tremendous gift that day. I was given a true under-standing of his side effects, of what it means to have grade 3 diarrhea, hemorrhoidal bleeding, and fecal incontinence. If there was any chance I did not believe patients before that day, I have always believed patients since—no need to bring me evidence in a little brown bag. Thanks. I'm good. By this point in my retelling of the story, William was nearly doubled-over in laughter, red-faced, and barely able to breathe or stay in his chair. Thus, our little ritual began. William continued to bring me gifts in brown paper bags at every visit for the rest of his time as my patient. Always small tokens. A pocket pack of Kleenex during cold season. A can ofsoup “to warm my hands,” which are perpetually cold during physical examinations. A small handmade Christmas ornament. Sometimes, he would put a bag inside a bag, inside a bag…laughing like an evil super villain, while I nervously unpacked his brown paper bags of torture. William elected to go to hospice care appropriately, living a few months with a good quality of life with home hospice. A few weeks after his passing, his son arrived at the registration desk and asked to speak with me. When I went to the front of the clinic to invite him back, to hug him, and tell him how much his father mattered to all of us at the cancer center, he handed me a brown paper bag. “He insisted” was all William's son said. I opened it, genuinely concerned what I might find this time, nervously peeking into the bag. It was a copy of William's obituary, thanking the cancer center for all the care we had shown him and for inviting him to be part of our lives as much as we were a part of his. This is the greatest gift—the gift of impact. Of knowing my care mattered, of knowing we were truly on the same care team. I carry my patients and their families with me through life, recalling their anecdotes, wisdoms, and warnings at just the right moments. I save their precious words in a box of cards I keep at my desk. I also have a collection of hilarious, insightful, peculiar, and profound assortment of little gifts that made a patient think of me—a curio of curiosities, a microcosm of my career. I think this is why patients give these small tokens in the first place—to make tangible the gratitude, the emotion, and the bond that is ex-changed between the patient and the oncologist. In giving, we are connected. Gifts speak for us when the weight of emotion and the vulnerability of truth are too much. A gift says “you matter in my life” as much as a gift says “I want you to feel how life altering the diarrhea I have been experiencing at home has been.” I have received both those gifts. They have changed me. So, I do not know—I am thinking maybe it is time I go back to plunging my hand straight in? Because in the end, somewhere down there at the bottom, that is where all the good stuff is hidden. Mikkael Sekeres: Welcome back to JCO's Cancer Stories: The Art of Oncology. This ASCO podcast features intimate narratives and perspectives from authors exploring their experiences in oncology. I am your host, Mikkael Sekeres. I am Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. Today, I am so excited to be joined by Dr. Stephanie Graff, Associate Professor of Medicine at Brown University and Director of the Breast Oncology Program at Brown University Health in Providence, Rhode Island, to discuss her Journal of Clinical Oncology article, "Brown Paper Bags." Our guests' disclosures will be linked in the transcript. Stephanie, I am so excited to have you here. Welcome to our podcast, and thank you for joining us. Dr. Stephanie Graff: It is such an honor to be here and to discuss this with you. Mikkael Sekeres: Stephanie, I have to say, I feel like I know you so well because I have read your writing over years, and there is an intimacy to how you write and an honesty to it where I really feel as if we are sitting together over a table drinking an International House of Coffee mocha blend, talking about our recent trip to Paris. But I am not sure all of our listeners know you quite as well, so I am wondering if you can tell us a little bit about yourself. Dr. Stephanie Graff: Sure. So I am on the JCO Art of Oncology editorial board, and live in Providence. So you and I have many shared interests. I love to write and I love to read, and I think that how you described my writing reflects my communication. I think that I tend to be really honest and open with patients about, about everything, about both myself and their disease. And I think that that is really what you are capturing in my story writing. I am an avid reader. I read just nonstop and write a variety of different styles of writing. I have written several breast cancer related texts, obviously academic papers. I have confessed to you in the past that I write poetry, but it is for myself. It is very unlikely to end up in the pages of JCO. I like writing stories like this when I feel like a story has been percolating in my mind for a while. Mikkael Sekeres: Boy, there is a lot of jumping off points I want to take from what you just said, of course. Maybe we can start with your writing process. What triggers a story and how do you face the dreaded blank page? Dr. Stephanie Graff: I think it is different for different stories. Often, it is something that has been the struggle or the relived experience that I keep turning over. And I find that like when I am walking my dog in the morning or when I am running on the treadmill, that sometimes the same moments keep coming back up in my mind: a difficult patient encounter, a heartwarming patient encounter, a challenging conflict with a peer or colleague. Those are the things that I keep going back to. And I think that as I go back to it over time, I craft that narrative. And crafting the narrative is also what helps me work through the story and cement it as a lesson that I learned from or that becomes a memory that is important to me, and ultimately makes it easy to just sit down and write, which is often, I do just sit down and write the whole story and it comes out pretty much in the form I end up submitting. But I think that that is because I have spent so much pre-contemplative thought before I get to pen to paper. Sometimes it is, with this story, and I think I had said this in my original cover letter with "Brown Paper Bags," one of my nurses, my nurse practitioner, actually had gotten a gift from a patient that was actually wildly inappropriate for her, both as a gift from a patient and for her as an individual. And she had like brought it back to our shared workspace and was like, "Guys, like, what do I do with this?" And it prompted all of us to share our stories of like really fantastic things that patients have given us, really weird things that patients have given us, and just to end up laughing hysterically about the funny moments and getting a little teary-eyed thinking about the way that we hold on to some of those memories. Mikkael Sekeres: I love that whole description. First of all, starting with your writing process. I think we all come out of a room sometimes where we have been meeting with a person, and our stomach just turns. There is something that did not sit right with us about the interaction or there is something that was really special about the interaction. And I think if we are thoughtful people and thoughtful doctors, we ruminate over that for a while and think to ourselves, “What was it that was really special about that, that really worked that I can actually apply to other patients?” Or, “What was it that did not work, that something that went south where I probably need to change my behavior or change how I am entering an interaction so that does not happen again?” Dr. Stephanie Graff: Yeah, I think about it like those, you know, I am sure you have the same experience I do that a lot of your early childhood memories are actually photos of your early childhood that you can remember more clearly because you have the picture of them, and certainly the same is true for my own children. But I think that having that description, that powerful visual description of a photograph from a moment, helps you cement that memory and treasure it. And I think that the same is true with writing, that when we have an experience that if we are able to make it tangible, write about it, turn it into a song, turn it into a poem, turn it into a piece of art, whether that is, you know, an interpretive dance or a painting, whatever your expression is, that is going to be something that becomes a more concrete memory for you. And so regardless of whether it is a good memory or a bad memory, I think sometimes that that is how we learn and grow. Mikkael Sekeres: I think that is spot on. I believe there are some theories of memory also that talk about accessing the memory over and over again so that you do not lose it and you do not lose the connections to it. And those connections can be other memories or they can be anything that occurred with our five senses when the event actually occurred. Dr. Stephanie Graff: Yeah. That- so one of my favorite books is Audrey Niffenegger's book called The Time Traveler's Wife. Have you read that? It is- the gentleman has a, you know, genetic condition in the fictional book that makes him travel in time and he like leaves his body, his clothes are on the floor and travels back and he is drawn to moments that are important to him. So he is drawn back constantly to the moment he met his wife, he is drawn back constantly to the moment his parents died. And I think that that is true, right? Our memory takes us back to those really visceral, important moments over and over again. Mikkael Sekeres: So you mentioned before, one of the jumping off points I wanted to explore a little bit more was when someone gets an unusual gift and brings it back to the workroom and there is that moment when everyone looks at it and the person says exactly what you said, "What do I do with this?" Right? And it is interesting that it is even a question because sometimes there is a really weird gift and there are certain people who would just immediately put it in the trash, but as oncologists, we do not, do we? Dr. Stephanie Graff: No. Mikkael Sekeres: That is not an option, but we want to know what it is we can do with it. So I do not know if you can remember any particularly unusual gifts you received or your colleagues received during that conversation and then what do you do with them? Dr. Stephanie Graff: Yeah, I think that sometimes they are, I mean, honestly, like the truth is is that I have them, right? Like they are all over my life, these little trinkets and doodads, even to the point that sometimes I give gifts that are inspired by my patients, too. Like two Christmases ago, I gave all of my colleagues as their Christmas gift these blown glass octopuses because one of my patients was obsessed with octopi and it like had led to several conversations, and they have obviously eight arms, we all know that, but they have numerous hearts, they have this very complex, empathetic brain, they are thinking and feeling, very cool, cool animals if you really start to learn and read about them. And I really started to think both about how much we had all kind of rallied around this one patient and her unique love of octopi, but also like how much that animal represents what it means to practice team based care, to have this larger than life heart, to feel like you are more than one brain, like you have eight arms because you work with these really great people. So I wrote that much more eloquently than I am doing right now in a card for my team and gave them these glass octopuses for Christmas. And so, you know, I think that our patients, it is not always even a physical gift. Sometimes it is just sharing their stories that ends up staying with us. Mikkael Sekeres: And that must not have been that long after the documentary was released about the man who had this special relationship with an octopus as well. So do you save the gifts given to you by patients? Why or why not? Dr. Stephanie Graff: So, obviously we get a lot of things like food and we just eat that, right? I am sure your clinic is a collection of boxes of chocolates and, so in Rhode Island, there is a lot of Portuguese patients and so we get a lot of like Portuguese bread and things like that too, which is delicious. So we have all sorts of food all the time and that just gets eaten. I do save patients'- and I realize we are not on camera for our viewing audience, but I have bizarrely, so one patient gave me this red devil, which is amazing because Adriamycin, which is obviously a really common breast cancer drug, is called the "red devil." And this is kind of a famous folk art carving by Alexander Girard. I think the actual real one is in Philadelphia at their art museum, but she was like, "You gave me the red devil, so I am going to give you the red devil." And like, I think that is hilarious. Like, I will save that forever. But I have so many other patients that have given me like little angels because I like meant a lot to them or helped them through this difficult moment. And I have all of those things, right? And so I have this kind of funny little shelf of angels and devils in my office, which is, I think, amusing. And then, obviously I wrote about the brown paper bags. You know, that patient filled it with little things like butterscotches and a can of soup and an instant hot cocoa mix. It was stuff that like you can realistically use. It kind of comes and goes. It is not necessarily something that you have forever. I had all three of my children during my time, one in fellowship and two as a practicing oncologist, and I was practicing in the Midwest then. I have a wealth of absolutely gorgeous quilts, baby quilts, that were made by my patients for my kids. And I have saved every single one of those. I can tell you which patient made it for which child because those are just such heirlooms to me. Yeah, lots of really great things. I am curious about you. You have to have these treasures too in your life. Mikkael Sekeres: Oh, absolutely. Isn't it remarkable that people in the face of life threatening illnesses, and I probably have a patient population specializing in acute leukemia and myelodysplastic syndromes where their illness is often more acute than, than your typical patient in your patient population even, but even during those times, I am always so moved how people take the time to ask about us and want to know about our lives as physicians and take the time to give a gift. And sure, I have my own shelf of curios, I think that is how you refer to it in your essay, from patients and it is very meaningful. There was one patient I treated who was a baseball fan. We were both living in Cleveland at the time. I am a Yankees fan. Both my parents are from the Bronx, so they raised me the right way, of course, even though I was raised in Providence, Rhode Island. And she was a Red Sox fan, and every time she came to visit me, she would wear red socks. It became this ongoing joke. She would wear her red socks and I would remember to wear my Yankees socks. So when we reached the five year mark, she was cured of her leukemia, she gave me a framed box of red socks to hang up. So, yeah, we have these stories and they are immediately evocative of the person we took care of and built a relationship, hopefully a long term relationship with. Gift giving in oncology can be nuanced at times. Why do you think patients give gifts and why are they meaningful to us as caregivers? Dr. Stephanie Graff: I mean, I think that gift giving at its heart is sometimes just a more comfortable way to express emotion for so many patients, right? And humans, right? We give gifts to celebrate births, weddings, birthdays, anniversaries, major holidays, right, for our own friends and family. And so it makes sense that that cultural or social tradition exists where we give gifts to acknowledge and celebrate that someone is important and a part of our life. And so often, I think it is just a way for a patient to say, "You have been here for me, I see you, I see the work you do, I appreciate you." So it is a way to say thank you that to any individual patient feels bigger than just the words. Obviously, I want to say as- if any patient stumbles onto this podcast, just the words are more than enough and we do not even need that. Like it is my greatest honor to care for the patients that allow me to enter their lives and care for them. Like, I do not need them to tell me thank you. I certainly do not need them to give me a gift, but I think that is a big part of why patients do it. But I think another part of it is that in many ways, you know, we have all seen that when somebody is diagnosed with cancer, that they have this real reckoning with their family and friends where people that they thought were very good friends do not know how to show up for them. And so sometimes they see these shifting dynamics in their friend groups, especially maybe for our younger patients or mid aged patients that just their friends are so busy. There is lots that goes on, right, that I think that often the gift is saying, "Thank you for showing up." We were a constant in their life during that time and for many of my patients, they do not have that constancy from the other people in their life. And so again, if anyone stumbles onto this podcast and someone in your life that you love is diagnosed with cancer, the most important thing that any of us can do for someone battling a chronic illness is just show up. And I often tell people even uninvited, like, show up and offer to take their laundry back to your house, show up and drop off a meal because I think that the people saying, "Well, let me know what I can do," is not helpful because it is really awkward to tell people what to do when you are battling an illness. Mikkael Sekeres: That notion of presence is just so important and you enunciated it beautifully. When my patients say to me, "Oh, I want to get you something," I always respond the same way that you do. I always say, "Your good health is the greatest gift that I could hope for," and just the, just the words and the presence are enough. I wanted to end quoting you to yourself and asking you to reflect on it. You write, "I carry my patients and their families with me through life, recalling their anecdotes, wisdoms, and warnings at just the right moments." Stephanie, what are those moments when you lean on the anecdotes and wisdom of your patients? Dr. Stephanie Graff: Patients will say things to me about - oh gosh, I will get all teary thinking about it - you know, patients say things to me who are my, you know, stage four metastatic patients about what has mattered to them in life. And it makes it so easy for me to leave that thing undone and go home at the end of the day because none of them say, "It really mattered to me that I spent that extra hour at work or that I got that promotion or that raise." I am in the habit of, when I meet patients for the first time and they are at a visit with their husband or their wife or their partner, I will ask how long they have been together. And when patients tell me that it has been decades, 40, 50, 60 years, I will ask what the secret is, because I am at 17 years of marriage and I'd love to see 63, which is my record for a patient story. And my one patient during a visit, the wife and I were talking and I asked how long they had been married. We had already had a pretty long visit at that point when it came up, and the whole visit, the husband had just sat in the corner, very quiet, had not said a word. For all I know, he could have been nonverbal. And she said, "Oh, we have been married 60 years." And I said, "Oh my gosh, what is the secret?" And before she could even open her mouth, he goes, "Separate bathrooms." I think about it all the time. Like any time I am like annoyed with my husband getting ready in the morning, I am like, "Yep, separate bathrooms. It is the key to everything." Bringing those little moments, those little things that patients say to you that just pop back up into your mind are so wonderful. Like those rich little anecdotes that patients share with you are really things that stay with you long term. Mikkael Sekeres: So it does not surprise me, Stephanie, that you and I have settled on the same line of questioning with our patients. I wrote an Art of Oncology piece a few years ago called exactly that: "What I Learned About Love From My Patients," asking the exact same question. It was a fascinating exploration of long term marriage from people who say, "Oh, you have to have a sense of humor," which you always hear, to some things that were just brutally honest where somebody said, "Well, I could not find anybody better, so I just settled," right? Because they are in the oncologist's office and sometimes people will speak very dark truths in our clinics. But my favorites were always the people where I would ask them and the husband and wife would turn to each other and just hold hands and say, "I do not know, I just love her." And I always thought to myself, that is the marriage for me. Dr. Stephanie Graff: My husband and I trained together. He was a fellow when I was a resident. So we had one rotation together in our entire careers and it was in cardiology. Like he was like the fellow on cardiovascular ICU and I was the resident on cardiology. And the attending had been prodding this woman who had heart disease about how she needed to be more physically active and said something to the extent to the patient about how he could tell that she was more of a couch potato, that she really needed to get more active. Mind you, this is a long time ago. And her husband, I mean, they are older patients, her husband boldly interrupts the attending physician and says, "She may be a couch potato, but she is my sweet potato." And my husband and I every once in a while will quip, "Well, you are my sweet potato" to one another because we still, we both remembered that interaction all these years later. Like, that is love. I do not know what else is love if it is not fighting for your wife's honor by proclaiming her your ‘sweet potato'. Mikkael Sekeres: Well, I cannot say just how much of a treat it has been to have you here, Stephanie. This has been Stephanie Graff, Associate Professor of Medicine at Brown University and Director of the Breast Oncology Program at Brown University Health in Providence, Rhode Island, discussing her Journal of Clinical Oncology article, "Brown Paper Bags." If you have enjoyed this episode, consider sharing it with a friend or colleague or leave us a review. Your feedback and support helps us continue to have these important conversations. If you are looking for more episodes and context, follow our show on Apple, Spotify, or wherever you listen and explore more from ASCO at asco.org/podcasts. Until next time, this has been Mikkael Sekeres. Thank you for joining us. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show Notes: Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Stephanie Graff, MD, FACP, FASCO is an Associate Professor of Medicine at Brown University and Director of Breast Oncology at Brown University Health in Providence Rhode Island Additional Reading: What My Patients Taught Me About Love, by Mikkael Sekeres

TTFields in Locally Advanced Pancreatic Adenocarcinoma

Play Episode Listen Later Sep 11, 2025 18:42

Host Dr. Shannon Westin and guest Dr. Hani Babiker discuss the JCO article "Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study." TRANSCRIPT TTFields in Locally Advanced Pancreatic Adenocarcinoma Dr. Shannon Westin: Hello everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth with manuscripts that have been published in the Journal of Clinical Oncology. I am your host, gynecologic oncologist Shannon Westin, social media editor at the JCO, and just excited to be here to learn today about pancreatic cancer. None of our participants have conflicts of interest related to this podcast, and it is my honor to introduce Dr. Hani Babiker. He is an associate professor of medicine, consultant in oncology at the Mayo Clinic in Jacksonville, Florida. Welcome, Dr. Babiker. Dr. Hani Babiker: Hi, Dr. Westin. Thank you for the great opportunity to discuss our trial, and thank you for having me here. I really appreciate it, and I am excited. Dr. Shannon Westin: All right, so are we. So we are going to be talking about “Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: A Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study.” This was simultaneously published and presented in the JCO and at the annual meeting of ASCO on 5/31/2025. So, let's level set. Can you speak to us just a little bit about pancreatic cancer? What is the survival, and what is the typical treatment for locally advanced disease? This gynecologic oncologist has not kept up in this field. Dr. Hani Babiker: Absolutely, Dr. Westin, and thank you for that question. Pancreatic adenocarcinoma is a lethal cancer. When I first started my career, the 5-year survival, per the Surveillance, Epidemiology, and End Results, was at 4.5%. I always, whenever I was giving talks, say that I really hope that I will see it in the double digit. Now, the 5-year survival for all pancreatic adenocarcinoma is 13.3%. And the 5-year survival, and although it is a double digit, I still hope that I will see it in a higher double digit in the future. It is even worse in patients with metastatic cancer, about 3% 5-year survival for metastatic pancreatic cancer. It is a dismal diagnosis. I really hope in the future we will find a better therapeutic approach to this lethal cancer. Dr. Shannon Westin: Yes, I just lost a very dear friend and colleague to this disease, so I completely agree with you. Well, now that we are settled kind of with the basics here, I would love to talk a little bit about kind of the primary piece of this intervention, the Tumor Treating Fields. So, how does this work? And what diseases has it gotten indications in as yet? Dr. Hani Babiker: Absolutely. So, Tumor Treating Fields is alternating frequency electrical fields that have been studied preclinically and shown that it abrogates cancer cell proliferation. Earlier on, we knew that it inhibits polymerization of tubulin, and hence, it affects cancer cells from proliferating. Later, we are learning that there are multiple mechanisms of action. It affects permeability, allowing for better drug delivery. It also inhibits cancer cell proliferation through affecting autophagy mechanisms that pancreatic cancer cells will use for proliferating and becoming more aggressive. There is also some early data preclinically in colorectal cancer cell lines and lung cancer cell lines and in vivo models showing that it potentially could activate the microenvironment to make it more pro-immunogenic. We recently published papers showing that it could also affect the nanomechanical properties of the tumor microenvironment within pancreatic cancer, hinting towards affecting, potentially, the stroma. So, there are multiple mechanisms to Tumor Treating Electric Fields. It is a new, novel therapeutic approach. Sometimes when I speak with my trainees, I say, "Well, we have surgery, we have radiation and chemotherapy, and this is something new." Tumor Treating Fields initially was studied in refractory GBM and got an indication there. Subsequently, frontline treatment of GBM in a randomized clinical trial, and then malignant pleural mesothelioma and non-small cell lung cancer. We have studied it in pancreatic cancer. Dr. Shannon Westin: I don't think I have ever heard it described so perfectly. That was brilliant. So thank you, and I hope everyone listening knows that you just got a masterclass on this mechanism. You know, they dabbled in it a little bit in ovarian cancer and it didn't quite make the grade, so I was a little definitely disappointed. But very excited about the data we're going to talk about today. So let's get into the PANOVA-3 study. Can you highlight the overall design and also the key eligibility criteria that would be helpful for our listeners? Dr. Hani Babiker: Absolutely. So, it started off with preclinical work in pancreatic cancer showing Tumor Treating Fields with chemo abrogate cancer cell perforation. It led to a trial, the PANOVA-2 trial, that was run in Europe that showed efficacy for OS and PFS in patients with locally advanced pancreatic cancer, which included metastatic and locally advanced pancreatic cancer, more so in locally advanced that led to the PANOVA-3 trial, which was an international, global study. This was in more than 190 centers, 20 countries in Latin America, North America, Europe, and Asia. It was a randomized trial. Patients were randomized 1 to 1 to either chemotherapy with gemcitabine plus nab-paclitaxel per drug label. The other arm was with Tumor Treating Fields at 150 kHz for a recommendation for patients to wear it 18 hours per day. The primary end point of the trial was OS, overall survival. The secondary end point included other efficacy landmarks such as local PFS, pain control, quality of life, and safety. And there was a post hoc that looked at distant PFS. Dr. Shannon Westin: That's a pretty common secondary end point in pancreatic studies of looking at the pain-free interval. I thought that was really brilliant because, you know, I think in gyn cancers, we see resolution of symptoms as being a really big deal, but it's not necessarily something that we always look at. So I thought that was really nice that you included that. Okay, talk to us a little bit about the population. So, the population that actually got treated in PANOVA-3 is pretty generalizable to what people are treating in the clinic. Dr. Hani Babiker: So, in pancreatic cancer, unfortunately, most of our patients present, approximately 80%, with metastatic disease. Local is divided to resectable, borderline, and locally advanced. We studied this trial, a randomized trial, in locally advanced and unresectable, which is really an unmet need. Most of our patients with locally advanced and unresectable are grouped up with other trials in the metastatic setting without a focus on locally advanced and unresectable, save for a few trials. This year, a trial that we were looking for for a long time, the LAPLACE trial, unfortunately, that we were very excited about, this is a molecule that targeted connective tissue growth factor, that showed earlier efficacy in a randomized trial, did not meet up the median OS end point. And hence, PANOVA-3 is the first trial in locally advanced and unresectable that did meet its primary end point. So, it's a very unmet need in locally advanced and unresectable. A lot of the times, our patients in clinic are treated with frontline chemotherapy that was studied in metastatic disease and locally advanced and unresectable, which include either FOLFIRINOX, NALIRIFOX, or gemcitabine/abraxane. I do have in my clinic multiple patients that would stay on the regimen for such a long time, and then we would have to devise a mechanism of maintenance, although this is not studied really in details, either with capecitabine or dropping the oxaliplatin to continue FOLFIRI. And then we also approach chemoradiotherapy. So the trial was in a disease in pancreatic cancer that really is an unmet need. So the inclusion criteria included a patient with locally advanced and unresectable. These were done at multiple centers. Most of them academic centers were discussed at the tumor board, and if it's unresectable, they will be meeting specific metrics of appropriate liver function tests, kidney function tests, and blood counts. We excluded patients that obviously had, given that these are electric fields, patients that have, for example, stimulators or pacemakers, knowing that this could potentially affect some of these devices. But for the most part, it was locally advanced and unresectable patients with a very good performance status and good counts. Dr. Shannon Westin: That's great. I think everyone's excited to hear about the primary outcome of overall survival. What did you find, and how does it compare to some of the recent trials? Dr. Hani Babiker: We're very excited that it did meet its primary end point of median overall survival. It was very exciting knowing that a lot of us were disappointed a little bit of some of the trials that were presented at ASCO GI, such as the LAPLACE trial that I alluded to. Just before the presentation, the PRODIGE 29 trial that is in locally advanced and unresectable that randomized patients with locally advanced disease to either FOLFIRINOX or single-agent gemcitabine, allowing for a crossover, although it did meet its primary end point of PFS, there was no overall survival benefit. So that kind of got us a little bit disappointed, but having the PANOVA-3 trial being positive in median OS got us all excited. In addition, the 12-year overall survival rate was increased in both the intention-to-treat and modified intention-to-treat. The modified intention-to-treat were patients that have had at least one cycle of therapy with TTFields daily and/or one cycle with chemotherapy, which was gemcitabine plus nab-paclitaxel. There was a trend to improvement in PFS and local PFS, although that did not have statistical significance, but the 12-year PFS rate in both the intention-to-treat and modified intention-to-treat was significant. For me, as one of the investigators, that told me that there might be a specific biomarker that would tell me that patients could respond greater than others, more exceptional than others, given that 12-month PFS rate was improved. On a post hoc analysis, the distant PFS was improved with the intervention of Tumor Treating Fields with gemcitabine plus nab-paclitaxel. In addition, there was an improvement in global health status and quality of life in addition to pain-free survival, which is a strong hurdle in our patients with pancreatic adenocarcinoma that most present with significant abdominal pain. Dr. Shannon Westin: One of the other questions that I think has come up is around central review. So did you all use central review in this study? Dr. Hani Babiker: Most of the centers were academic centers. These were discussed in tumor boards, which included radiation oncologists and surgeons. I wanted to point out that it's very important to note that the primary end point was overall survival. So the primary end point was not PFS. Hence, the central review would help us, for example, with elaborating and making sure patients were actually locally advanced disease, but in a setting where the primary end point is overall survival, that was the key point of the clinical trial. This trial was discussed at academic centers, and all included tumor boards to decide if patients were locally advanced or not. In the trial, there was a good proportion of patients, or percentage, that had a CA 19-9 more than 1000. That could indicate that potentially there are a fraction of patients that actually had metastatic disease, micrometastatic disease. So that could hint towards why the median OS was slightly lower then in both arms when compared to, for example, the trial that was presented at ASCO GI, the LAPLACE trial. However, having said that, we were very excited about the trial. It was the first positive trial in locally advanced and unresectable to meet median OS survival. Dr. Shannon Westin: It's so awesome. So congratulations. Okay, so let's talk a little bit about your very detailed secondary end points because you had a lot of really prudent choices there. So anything that was interesting or informative in those end points? Dr. Hani Babiker: One major hurdle back we have for most of our patients with pancreatic adenocarcinoma, like I mentioned earlier, is pain. We try to approach it, obviously, with narcotics. If it doesn't work, we try to do celiac axis block interventionally, and that sometimes is successful and sometimes is not. So actually, to see the pain-free survival end point to be met was very exciting for us. And as for me, as a scientist that studies TTFields in clinic and lab as also to develop a mechanism and understanding really how that works. That was very important for us that in addition to chemotherapy, it improved pain-free survival or deterioration of pain. And most importantly, our patients with pancreatic cancer, this disease is very aggressive. It affects quality of life of patients. Patients feel fatigued, tired. It's a procoagulant tumor that causes clots and strokes, etcetera, marantic endocarditis. And one big problem we deal with when we're seeing patients in clinic is obviously that quality of life. Although data have shown with treatment, with frontline regimens, that quality of life improves with treatment and chemotherapy, it's actually great to see that that improvement happens early in addition to Tumor Treating Fields. The other interesting point was that it was not only pain and quality of life, but also digestive symptoms that are improved with this intervention, knowing that a lot of our patients do have pancreatic cancer, pancreatic exocrine insufficiency that affect also with digestion, and a lot of our patients have abdominal pain after eating and diarrhea. So it was interesting to see that also improved with the intervention. Dr. Shannon Westin: You have touched a little bit on some of the adverse events, kind of with the TT mechanisms, but I'd love to hear a little bit more detail around adverse events in general in this study, as well as specific AEs related to the Tumor Treating Fields. Dr. Hani Babiker: Absolutely. So when we compared both arms, there was a similar toxicity related to the regimen, mostly with chemotherapy, but in specifically to Tumor Treating Fields, there was a rash, and that included dermatitis and rash. Most of the side effects were grade 1 and grade 2. Grade 3 toxicities related to skin was less than 10%, approximately 7% to 8%, and hence did not affect many patients. But it was something to note, and it's something that in the future, when we develop a mechanism of treating patients to note early. We in our clinic have learned to treat patients in the clinical trial early with topical steroids to each patient, of shifting the arrays to mitigate some toxicity and rash. We do advise our patients in hot areas, we keep them aware that sweating, for example, can lead to higher conductivity of electrical fields with a predisposition for rash. So if there's an opportunity to stay in a little bit of a cold area, make sure that the arrays are shifted, use topical steroids early. If it's a significant rash, to hold treatment for at least 48 hours and speak to the investigators. And through these mechanisms, we have learned that we were able to mitigate the rash quite a bit. Dr. Shannon Westin: That's awesome. Thank you so much. Yeah, I'm, it's summer right now, and I think- I'm in Texas, you're in Florida, like we know. Okay, so I guess, again, you have been kind of touching on this, but I would love to know, like if in the quality-of-life assessments or if just in your discussions with patients, like how easy is this to use? How easy is the Tumor Treating Fields device to use, and what do patients really think? Dr. Hani Babiker: Absolutely. We have learned that whenever we speak with patients, it's always good to discuss with them briefly the science of it. A lot of patients would want to know if it's interventional, is that something that goes, is delivered percutaneously or not, and we explain that these are delivered through arrays that are through the skin. We always touch base with them about a lot of question I get about mechanism of action and then about compliance. So I think one important thing to note is that compliance with the use of the device is a lot of the question we'll get quite a bit. Patients know there's going to take an effort from them, and some of my patients enjoyed it because they felt like they also are fighting the disease by wearing the device. I have learned very quickly that having a team, surrounded by a team that knew how to mitigate some of the side effects and knew how to explain how to use the device helped quite a bit. And this included some of our nurses and our nurse practitioners and our clinical research coordinators who've done a wonderful job of showing these arrays actually to patients before they start on the trial, look at it, know how it works. The other point to know is that the sponsor provided Device Support Specialist, we call them DSS, they have been instrumental in helping us, helping the patients know how to use the device, how to use the generator, how to change the batteries, and that helped us conduct the trials and enroll very well. I would envision in the future with education and relying on the Device Support Specialist and having a team that knows how to use the device and mitigate some of the side effects will go a long way for patients to learn about this treatment. Many of the times our patients said while they are on the clinical trial felt like they are also being part of this team in applying the device and fighting the cancer. Dr. Shannon Westin: That's awesome. Well, I guess the bottom line. Is it ready for prime time? Is this something you are going to use for your patients in the clinic? Dr. Hani Babiker: Absolutely. In a disease that has poor prognosis, and we are trying our best to find new treatments to fight this cancer and treatment modalities, presenting patients with all the treatment options that are out there would be recommended. It's what I would do it for in my clinic. And you know, it's funny that I am mentioning that right now. I had a patient who was seen internationally asking about the trial and the device and had locally advanced and unresectable before they start frontline treatment. I do think that there is going to be an educational piece. Obviously, this is not a pill, it's not an intravenous chemotherapy that we're very well and accustomed to. And some of us in academic centers know it very well. I usually joke that whenever I am talking about it in pancreatic cancer, if there is a radiation oncologist in the room, they will be like, "Yeah, we know all about it. We have been treating patients with GBM over there." So a lot of the times, when we first went to trial, if I had any questions, I would call them and ask them. So from their perspective, they, because they use it as a standard of care in treatment of GBM, they develop significant expertise in it. I think in the GI world, specifically and with oncologists that treat pancreatic cancer and specifically oncologists in the community, learning about the device and how to use it, how to recommend it, how to mitigate side effects, will be hopefully for prime time in the future. Dr. Shannon Westin: That's great. Sounds like some real educational opportunities there. Well, this has been awesome. Thank you so much, Dr. Babiker. I mean, I learned a ton, and I wish that we could find a way to use this in gynecologic cancers, but really, really just want to commend you on the design of the trial and the success in this really devastating disease. So again, this was "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: A Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study." And as always, I am your host, Shannon Westin. Please go check out our other offerings wherever you get your podcasts and have an awesome day. 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. Babiker Disclosures Consulting or Advisory Role: Endocyte, Celgene, Idera, Myovant Sciences, Novocure, Ipsen, Caris MPI, Incyte, Guardant Health Speakers' Bureau: Guardant Health Research Funding: Spirita Oncology, Novocure, AstraZeneca, JSI, Incyte, Qurient, HiFiBiO Therapeutics, Revolution Health Care, Elevation Oncology, Dragonfly Therapeutics, Zelbio, BMS, Mirati Therapeutics, Strategia

texas europe local study north america journal patients os latin america jacksonville grade gi surveillance astrazeneca mayo clinic locally tt epidemiology subsequently laplace strategia asco aes bms pancreatic dss pfs gbm clinical oncology khz prodige ipsen jsi celgene jco adenocarcinoma incyte open label gemcitabine folfirinox mirati therapeutics asco gi elevation oncology idera folfiri ttfields

JCO at WCLC: Multinational Pivotal Study of Sunvozertinib in Exon20ins NSCLC

Play Episode Listen Later Sep 9, 2025 7:45

JCO fellow Dr. Ece Cali speaks with JCO Associate Editor Dr. Thomas E. Stinchcombe to discuss the JCO article "Phase 2 Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B)", that was simultaneously released at the IASLC 2025 World Conference on Lung Cancer. TRANSCRIPT Dr. Ece Cali: Hello, and welcome to our series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's most important oncology meetings. I am your host, Dr. Ece Cali, JCO editorial fellow, and I am joined by Dr. Tom Stinchcombe, JCO associate editor, to discuss the Journal of Clinical Oncology article and 2025 World Conference on Lung Cancer abstract presentation, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non–Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” The WU-KONG1B trial is a multinational, phase II study that investigated the efficacy and safety of different doses of sunvozertinib in patients with metastatic non-small cell lung cancer and EGFR exon 20 insertion mutations after progression on platinum based chemotherapy. Tom, before we dive into the results, could you walk us through the rationale for this study, and how does it fit into the current treatment options for patients with EGFR exon 20 insertion? Dr. Tom Stinchcombe: Thank you, Dr. Cali. I think the clinical context is always important. We have known that EGFR exon 20 insertions exist and that they are resistant to our currently available EGFR tyrosine kinase inhibitors, and I think there have been attempts in the past to develop a tyrosine kinase inhibitor, but there is a very narrow therapeutic window between the dose you need to inhibit the EGFR mutation in the cancer and the EGFR receptor on normal tissues, most notably the mucosa, the gut, and the skin. And so, our previous attempts have failed largely because the dose required was not tolerable for patients and they could not really stay on the drug for a long time or they were not very active. And so, I think there was a real desire to develop an EGFR tyrosine kinase inhibitor, and then, historically, the standard had been a platinum based doublet as the standard of care. And more recently, platinum based doublet with amivantamab has proven to be superior to platinum based chemotherapy alone. I think the context is also important that amivantamab is not necessarily available in all the countries, and so, there are patients who do not have access to amivantamab. Going to the rationale, I think that this drug had shown preliminary promise of having activity but without that being encumbered by those EGFR wild type toxicities, and, therefore, it was really explored in this larger study. Dr. Ece Cali: And what are some key findings from this trial? Dr. Tom Stinchcombe: So, I think that we should look at the study design. It is a little quirky, for lack of a better term, in that there is a randomization to 200 versus 300 mg, and then, there was a nonrandomized cohort of 300 mg. So, when you look at the study, if you are a purist, you will just look at the randomized patients. If you are sort of an aggregator, you look at all patients. So, it shows reporting on three cohorts, but I think the key findings are that the 200 mg and the 300 mg treatments had similar toxicities in terms of response rate, duration of response, and progression free survival. And as you know going through the review, there was a lot of queries from the reviewers as to which would be the preferred dose, and to me, I think this really illustrates a dose finding component to a trial design because there is a lot of debate about what the minimal effective dose is or the optimal dose. And in this case, having the two dose cohorts did provide us some valuable efficacy and toxicity information. And then, when I look at the study, I want to make sure it reflects my patient population, and about a quarter of patients had brain metastases, and about 15% had previous amivantamab, and about 5% to 10% had another EGFR tyrosine kinase inhibitor. Dr. Ece Cali: And what is the objective response rate and the duration of response? These are pretty good numbers for this patient population. Dr. Tom Stinchcombe: In the 200 mg cohort, it was about 46%. The duration of response was around 11 months, and the PFS was around 8 months. The 300 mg cohort was 46%, duration of response 9.8, and the median PFS is 6.9 months, and I think that this is greater activity than we have seen with our previous attempts at EGFR tyrosine kinase inhibitors. Dr. Ece Cali: And based on these data, FDA granted accelerated approval for sunvozertinib very recently at 200 mg once daily dosing in this setting. So, that is a major step forward for our patients. Dr. Stinchcombe, how does this impact your clinical practice, and what side effects should oncologists be watching for if they prescribe this medication? Dr. Tom Stinchcombe: So, I think it was very interesting that they chose the 200 mg dose, which I think was more tolerable, and when we kind of look at this, there still was a rate of diarrhea, all grade, rash, paronychia, which are the EGFR related toxicities. There can be some decreased appetite, stomatitis, and then, it can lead to some lab abnormalities, like increased CPK and creatinine that physicians have to be aware of. You know, how it will affect my practice is that all these patients had received a platinum based chemotherapy as the first line therapy. I think that this would become my preferred second line therapy for patients outside the context of a trial because of the activity and the tolerability. Dr. Ece Cali: And lastly, several other tyrosine kinase inhibitors are being evaluated for EGFR exon 20 insertion, including in the frontline setting. So, what are some of the outstanding questions in this space, and what data should our listeners keep an eye on moving forward? Dr. Tom Stinchcombe: I think you are right that now, there is going to be another EGFR tyrosine kinase that may become available in the next year, and there is another drug, furmonertinib, that is being investigated. I think, for the clinical question, is, well, can we move these into the first line setting? And actually, the development path has two ways of doing this. There is EGFR tyrosine kinase compared to platinum based chemotherapy, and then, platinum based chemotherapy with an EGFR tyrosine kinase versus platinum based chemotherapy, and both have their merits and strengths. And so, I think it is going to be very interesting as we see if those first line trials, one, can they be demonstrated to be superior to platinum based chemotherapy, and then by what magnitude and what the side effects are. But I think we are hoping that in the next couple of years, we will have an additional first line option for our patients. Dr. Ece Cali: Yeah, it is always great to have more options for our patients. Thank you, Dr. Stinchcombe, for speaking about the JCO article, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” Join us again for the latest JCO simultaneous publications. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of World Lung Conference. 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.

study journal phase fda pivotal lung cancer asco multinational pfs egfr clinical oncology world conference nsclc cpk jco wclc transcript dr

Time to Cilta-Cel-ebrate?

Play Episode Listen Later Sep 4, 2025 10:25

The 5-year+ follow-up from CARTITUDE-1 has people asking if cilta-cel can cure multiple myeloma? We discuss this data and the broad comparison to the other BCMA-targeting CAR-T product, idi-cel and a recent comparison on plasma cell leukemia. CARTITUDE-1 Long-Term F/U: https://doi.org/10.1200/JCO-25-00760 Cilta-cel & ide-cel in plasma cell leukemia: https://doi.org/10.1182/bloodadvances.2025016966

cart jco bcma

No Versus Know: Patient Empowerment Through Shared Decision Making

Play Episode Listen Later Sep 2, 2025 28:38

Listen to ASCO's JCO Oncology Practice Art of Oncology article, "No Versus Know: Patient Empowerment Through Shared Decision Making” by Dr. Beatrice Preti, who is an Assistant Professor at Emory University. The article is followed by an interview with Preti and host Dr. Mikkael Sekeres. Dr Preti explores the challenges which may prevent oncologists from fully engaging with patients during shared decision making. TRANSCRIPT Narrator: No Versus Know: Patient Empowerment Through Shared Decision Making, by Beatrice T.B. Preti, MD, MMed, FRCPC During a recent clinic, I saw three patients back-to-back, all from minority backgrounds, all referred for second opinions, all referenced in the notes for being different forms of difficult. Refused chemo, refused hospice, read one note. Refused surgery and chemo, read another, unsure about radiation. Yet, despite the documented refusals (I prefer the term, decline), they had come to my clinic for a reason. They were still seeking something. As an oncologist trained in a program with a strong emphasis on shared decision making between physician and patient, I approach such situations with curiosity. I consider optimal shared decision making a balance between the extremes of (1) providing a patient complete choice from a menu of treatment options, without physician input, and (2) indicating to a patient the best course of treatment, in the eyes of the physician.1 This is a balance between beneficence (which can often turn paternalistic) and patient autonomy and requires a carefully crafted art. Many of my consults start with an open question (Tell me about yourself…?), and we will examine goals, wishes, and values before ever touching on treatment options. This allows me to take the knowledge I have, and fit it within the scaffold of the patient in front of me. A patient emphasizing quantity of life at all costs and a patient emphasizing weekly fishing trips in their boat will receive the same treatment option lists, but with different emphases and discussions around each. Yet, many physicians find themselves tending toward paternalistic beneficence—logical, if we consider physicians to be compassionate individuals who want the best for their patients. All three patients I saw had been offered options that were medically appropriate, but declined them as they felt the options were not right for them. And all three patients I saw ended up selecting a presented option during our time together—not an option that would be considered the best or standard of care, or the most aggressive treatment, but an option that aligned most with their own goals, wishes, and values. This is of particular importance when caring for patients who harbor different cultural or religious views from our own; western medicine adopts many of its ideas and professional norms from certain mindsets and cultures which may not be the lenses through which our patients see the world. Even when a patient shares our personal cultural or religious background, they may still choose a path which differs from what we or our family might choose. It is vital to incorporate reflexivity in our practice, to be mindful of our own blinders, and to be open to different ways of seeing, thinking, and deciding. I will admit that, like many, I do struggle at times when a patient does not select the medically best treatment for themselves. But why? Do we fear legal repercussions or complaints down the road from not giving a patient the standard of care (often the strongest treatment available)? Do we struggle with moral distress when a patient makes a choice that we disagree with, based on values that we ourselves do not hold? Do we lack time in clinics to walk patients through different options, picking the method of counseling that allows the most efficiency in packed clinical systems? Is it too painful a reminder of our mortality to consider that, especially in the setting of terminally ill patients, aiming for anything other than a shot at the longest length of life might be a patient's preference? Or are we so burnt out from working in systems that deny us sufficient choice and autonomy (with regards to our own work, our own morals, and our own lives) that, under such repeated traumas, we lose touch with the idea of even having a choice? I have a number of patients in my clinic who transferred care after feeling caught between one (aggressive) treatment option and best supportive care alone. They come looking for options—an oral agent that allows them to travel, a targeted therapy that avoids immunosuppression, or a treatment that will be safe around dogs and small children. They are looking for someone to listen, to hold their hand, to fill in the gaps, as was told to me recently, and not skirt around the difficult conversations that both of us wish we did not have to have. Granted, some of the conversations are challenging—requests for ivermectin prescriptions, for example, or full resuscitation efforts patients with no foreseeable chance of recovery (from a medical standpoint) to allow for a possible divine miracle. However, in these cases, there are still goals, wishes and values—although ones that are not aligned with evidence-based medical practice that can be explored, even if they are challenging to navigate. As my clinic day went on, I spoke with my patients and their loved ones. One asked the difference between hospice and a funeral home, which explained their reluctance to pursue the former. Another asked for clarification of how one treatment can treat cancer in two different sites. And yet still another absorbed the information they requested and asked to come back another day to speak some more. All questions I have heard before and will continue to hear again. And again. There is no cure for many of the patients who enter my GI medical oncology clinic. But for fear, for confusion, perhaps there is. Cancer wreaks havoc on human lives. Plans go awry, dreams are shattered, and hopes are crushed. But we can afford some control—we can empower our patients back—by giving them choices. Sometimes, that choice is pitiful. Sometimes, it is an explanation why the most aggressive treatment option cannot be prescribed in good faith (performance status, bloodwork parametres), but it is a choice between a gentle treatment and no treatments. Sometimes it is a choice between home hospice and a hospice facility. I teach many of the learners who come through my clinic about the physician's toolbox, and the importance of cultivating the tools of one's specific specialty and area of work. For some (like surgeons), the tools are more tangible—physical skills, or even specific tools, like a particular scalpel or retractor. For others, like radiologists, it might be an ability—to recognize patterns, for example, or detect changes over time. For those of us in medical oncology, our toolbox can feel limiting at times. Although we have a handful of treatments tied to a specific disease site and histology, these often fall short of what we wish we could offer, especially when studies cite average survivals in months over years. But one of our most valuable tools—more valuable, I would argue, than any drug—is the communication we have with our patients, the way we can let them know that someone is there for them, that someone is here to listen, and that someone cares. Furthermore, the information we share—and the way we share it—has the potential to help shape the path that our patient's life will take moving forward—by empowering them with information to allow them to make the decisions best for them.2 Although having such conversations can be difficult and draining for the oncologist, they are a necessary and vital part of the job. My clinic team knows that we can have up to six, seven such conversations in the course of a half-day, and my clinic desk space is equipped for my between-patient routine of sips of tea and lo-fi beats, a precious few moments left undisturbed as much as possible to allow a bit of recharging. By finding a safe space where I can relax for a few moments, I can take care of myself, enabling me to give each of my patients the time and attention they need. When patients thank me after a long, difficult conversation, they are not thanking me for sharing devastating, life-altering news of metastatic cancer, prognoses in the order of months, or disease resistant to treatment. They are thanking me for listening, for caring, for seeing them as a person and affording the dignity of choice—autonomy. I have had patients make surprising decisions—opting for no treatment for locally-advanced cancers, or opting for gentle treatment when, medically, they could tolerate stronger. But by understanding their values, and listening to them as people, I can understand their choices, validate them, and help them along their journey in whatever way possible. Providing a choice affords a suffering human the right to define their path as long as they are able to. And we can give patients in such situations support and validation by being a guide during dark days and challenging times, remembering that medically best treatment is not always the best. When a patient says no to offered options, it does not (necessarily!) mean they are rejecting the expertise of the physician and care team. Rather, could it be a request to know more and work together with the team to find a strategy and solution which will be meaningful for them? Mikkael Sekeres: Welcome back to JCO's Cancer Stories: The Art of Oncology. This ASCO podcast features intimate narratives and perspectives from authors exploring their experiences in oncology. I'm your host, Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. Today we're joined by Beatrice Preti, Assistant Professor at Emory University, Adjunct Professor at Western University, and PhD candidate with Maastricht University, to discuss her JCO Oncology Practice article, "No Versus Know: Patient Empowerment Through Shared Decision-Making." At the time of this recording, our guest has no disclosures. Beatrice, thank you so much for contributing to JCO Oncology Practice and for joining us to discuss your article. Beatrice Preti: Well, thank you so much for having me today. Mikkael Sekeres: It's an absolute treat. I was wondering if we could start with sort of a broad question. Can you tell us about yourself? What was your journey like that landed you where you are right now? Beatrice Preti: Oh goodness, that's a very loaded question. Well, I am originally from Canada. I did all my training in Canada at a couple of different schools, McMaster, Queens, Western University. Before medicine, I was always interested in the arts, always interested in writing, always interested in teaching. So that's something that's really, I guess, come forth throughout my medical practice. During my time at Western, I trained as a gastrointestinal medical oncologist, so that's my clinical practice. But on the side, as you've noted, I've done some work in medical education, got my Masters through Dundee, and now doing my PhD through Maastricht in the Netherlands, which I'm very excited about. Mikkael Sekeres: That's fantastic. What's your PhD in? Beatrice Preti: Health Professions Education. Mikkael Sekeres: Wonderful - can never get too much of that. And can I ask, are you at the stage now where you're developing a thesis and what's the topic? Beatrice Preti: Yeah, absolutely. So the program itself is almost exclusively research based. So I'm thinking of more of a social psychology side, looking at impression management and moral distress in medical trainees, and really along the continuum. So what we're looking at is when people act in ways or feel that they have to act in ways that aren't congruent with what they're feeling inside, why they're doing that and some of the moral tensions or the moral conflicts that go along with that. So a good example in medicine is when you're with a patient and you have to put on your professional face, but inside you might be squirming or you might be scared or worried or anxious or hungry, but you can't betray that with the patient because that would be unprofessional and also unfair to the patient. Mikkael Sekeres: Wow, that's absolutely fascinating. How does that change over the course of training? So how does it change from being a medical student to a resident or fellow to a junior faculty member? Beatrice Preti: So I'm only one year into the PhD, so I don't have all the information on this as yet. Mikkael Sekeres: You don't have all the answers yet? What are you talking about? Beatrice Preti: Yeah, they're telling me I have to finish the PhD to get all the answers, but I think that we certainly are seeing some kind of evolution, maybe both in the reasons why people are engaging in this impression management and the toll it takes on them as well. But stay tuned. It might take me a couple of years to answer that question in full. Mikkael Sekeres: Well, I just wonder as a, you know, as a medical student, we go into medical school often for reasons that are wonderful. I think almost every essay for somebody applying to medical school says something about wanting to help people, right? That's the basis for what draws us into medicine. And I wonder if our definition of what's morally right internally changes as we progress through our training. So something that would be an affront to our moral compass when we start as a medical student may not be such an affront later on when we're junior faculty. Beatrice Preti: Yes, definitely. And I think there's a lot of literature out there about coping in the medical profession because I think that by and large, especially in the lay community, so premedical students, for example, but even within our own profession as well, we don't really give enough credence to the impact a lot of the things that we do or witness have on us personally. That lack of insight doesn't allow us to explore coping mechanisms or at least think things through, and oftentimes what we're seeing is a survival instinct or a gut reaction kick in rather than something that we've carefully thought through and said, you know, “These situations are stressful for me, these situations are difficult. How can I cope? How can I make this more sustainable for me, knowing that this is an aspect of medicine that really isn't escapable.” Mikkael Sekeres: What a fascinating topic and area to be studying. I can't wait for all of the findings you're going to have over the course of your career. But oncology is a field that's, of course, rife with these sorts of conflicts. Beatrice Preti: Yeah, definitely. Mikkael Sekeres: I'm curious if you can talk a little bit about your own story as a writer. You say you've always been a writer. How long have you been writing reflective pieces? Beatrice Preti: Oh, goodness. So there's certainly a difference between how long I've been writing reflective pieces and how long I've been writing good reflective pieces. I can vaguely remember, I think being perhaps 10 years old and writing in school one recess period, sort of both sides of a loose leaf piece of paper, some form of reflection that would have ended up straight in the rubbish bin. So that was probably when it started. Certainly in medical school, I published a fair bit of reflective writing, poetry. That continued through residency, now as a junior attending as well. Mikkael Sekeres: Well, you're excellent at it and I can't see any rubbish can that would accept your pieces for the future. If you feel comfortable doing so, can you tell us what prompted you to write this particular piece? Beatrice Preti: Yes. So this piece was written Friday night around 9:00, 10:00 at night, literally at the end of the clinic day that I described. Coming on the heels of talking about coping, I think for many people in medicine, writing is a coping mechanism and a coping strategy that can be quite fruitful and productive, especially when we compare it to other potential coping strategies. Sometimes it's certainly difficult to write about some of the things we see and certainly it's difficult sometimes to find the words. But on this particular night, the words came quite easily, probably because this is not an isolated incident, unfortunately, where we're seeing patients coming for second opinions or you're encountering patients or you're encountering people who you are not directly treating in your everyday life, who express frustrations with the health care system, who express frustrations with not feeling heard. I think all you have to do is open social media, Facebook, Reddit, and you'll see many, many examples of frustrated individuals who felt that they weren't heard. And on one hand, I'm not naive enough to think that I've never left a patient encounter and had that patient not feeling heard. I'm guilty of many of the same things. Sometimes it's nothing that we've done as physicians, it's just you don't develop a rapport with the patient, right? But it made me think and it made me wonder and question, why is there this mismatch? Why are there so many patients who come seeking someone who listens, seeking a solution or a treatment that is maybe not standard, but might be a better fit for them than the standard? As you know, oncology is very algorithmic, and certainly, as many of the the fellows and residents who come into my clinic learn, yes, there are guidelines and yes, there are beautiful flow charts that teach us if you have this cancer, here's the treatment. But for me, that's only half of the practice of oncology. That's the scientific side. We then have the art side, which involves speaking to people, listening to them, seeing them as people, and then trying to fit what we're able to do, the resources we have, with what the patient's goals are, with their wishes or desires are. Mikkael Sekeres: I completely agree with you. I think sometimes patients come to our clinics, to an examination room, and they look at it as a place to be heard, and sometimes a safe space. You'll notice that, if you've been practicing long enough, you'll have some couples who come in and one of our patients will say something and the partner will reflect and say, "Gee, I never heard you say that before. I never knew that." So if people are coming in expecting to be heard in a safe space, it's almost nowhere more important to do that when it comes to treating their cancer also. Beatrice Preti: Yes. And as I say again to many of our learners, different specialties have different tools to treat or help alleviate sickness, illness, and suffering. For example, a surgeon has quite literal tools. They have their hands, they have their eyes, they're cutting, they're performing procedures. By and large, especially in medical oncology, we are quite limited. Certainly I have medications and drugs that I can prescribe, but in the world of GI oncology, often these are not going to lead to a cure. We are talking about survival in the order of months, maybe a year or two if we're very lucky. So the tool that we have and really the biggest, best treatment that we can give to our patients is our words and our time, right? It's those conversations that you have in clinic that really have the therapeutic benefit or potential for someone who is faced with a terminal illness and a poor prognosis more so than any drug or chemotherapy that I can give as a physician. Mikkael Sekeres: I love the notion that our words and our time are our tools for practicing medicine. It's beautiful. You mentioned in your essay three patients who, quote, and you're very deliberate about using the quote, "refused" because it's a loaded term, "refused" recommended medical intervention such as chemotherapy or surgery. Can you tell us about one of them? Beatrice Preti: Ah, well, I would have to be quite vague. Mikkael Sekeres: Of course, respecting HIPAA, of course. We don't want to violate anything. Beatrice Preti: But I think that was another thing too on this day that struck me quite a bit that it was three patients back to back with very similar stories, that they had been seen at other hospitals, they had been seen by other physicians - in one case, I think a couple of different physicians - and had really been offered the choice of, “Here is the standard of care, here is what the guidelines suggest we do, or you can choose to do nothing.” And certainly in the guidelines or in recommended treatment, you know, doublet chemotherapy, triplet therapy, whatever the case may be, this is what's recommended and this is what's standard. But for the patient in front of you, you know, whose goal may be to go to the beach for two months, right? “I don't want to be coming back and forth to the cancer center. Can I take a pill and maybe get blood work a few times while I'm there?” Or you have a patient who says, “You know, I tried the chemotherapy, I just can't do it. It's just too strong. And now they've told me I have to go to hospice if I'm not going to take the recommended treatment.” While in the guideline this may be correct for this patient who's in front of you, there may be another option which is more, in quotes, “correct”, because, is our goal to kill as many cancer cells as we can? Is our goal to shrink the cancer as much as we can? Is our goal even to eke out the maximum survival possible? As an oncologist, I would say no. Our goal is to try to line up what we can do, so the tools, the medications, the chemotherapies, the drugs that we do have in our tool kit, and the symptom medications as well, and line those up with what the patient's goals are, what the patient's wishes are. For many people, I find, when faced with a terminal illness, or faced with an illness with poor prognosis, their goal is not to eke out the last breath possible. They start to look at things like quality of life. They start to look at things like hobbies or travel or spending time with family. And oftentimes, the best way to facilitate that is not by doing the most aggressive treatment. Mikkael Sekeres: In my memory, you evoke an essay that was written for JCO's Art of Oncology by Tim Gilligan called "Knuckleheads" where he had a patient who was, big quotes, "refusing" chemotherapy for a curable cancer. And one of his colleagues referred to the patient as a knucklehead and they asked Tim to see the patient to try to suss out what was going on. And Tim, he used one of our tools. He talked to the person and it turns out he was a seasonal construction worker and it was summer and he was a single dad where the mother of his children wasn't involved in their care at all. And the only way he had to make money during the year was the work he did during the summer because he couldn't work in the winter. So for very primal reasons, he needed to keep working and couldn't take time to take chemotherapy. So they were able to negotiate a path forward that didn't compromise his health, but also didn't compromise his ability to make a living to support his family. But again, like you say, it's that people bring to these interactions stories that we can't even imagine that interfere with our recommendations for how they get cared for. Beatrice Preti: That's a beautiful example of something that I really do try to impress on my learners and my team in general. When someone comes to you and if a recommendation is made or even if they are skeptical about a certain treatment pathway, there is always a ‘why'. One of the challenges and one of the things that comes with experience is trying to uncover or unveil what that ‘why' is because unless you address it and address it head on, it's going to be very difficult to work with it, to work with the patient. So as you said, it's common people have family obligations, job obligations. Oftentimes as well, they have personal experience with certain treatments or certain conditions that they're worried about. Perhaps they had a loved one die on chemotherapy and they're worried about toxicities of chemo. And sometimes you can talk through those things. That needs to be considered, right? When we talk about shared decision-making, you, the patient, and it might be an experience that the patient has had as well that are all in the room that need to be taken into account. Mikkael Sekeres: You invoke the phrase "shared decision-making," which of course, you talk about in your essay. Can you define that for our listeners? What is shared decision-making? Beatrice Preti: Oh, goodness. There are different definitions of this and I am just cringing now because I know that my old teachers will not be happy regardless of what definition I choose. But for me, shared decision-making means that the decision of what to do next, treatment along the cancer journey, etc., is not decided by only one person. So it is not paternalism where I as the physician am making the decision. However, it's not the patient unilaterally making their own decision as well. It's a conversation that has to happen. And oftentimes when I'm counseling patients, I will write down what I see as potential treatment options for this patient and we will go through them one by one with pros and cons. This is usually after an initial bit where I get to know the patient, I ask them what's important to them, who's important in their life, what kind of things do they enjoy doing, and trying to weave that into the counseling and the discussion of the pros and cons. Ultimately, the patient does make the choice, but it's only after this kind of informed consent or this informative process, I guess, so to speak. And for me, that is shared decision-making where it's a conversation that results in the patient making a decision at the end. Mikkael Sekeres: You know, it's so funny you use the word ‘conversation'. I was going to say that shared decision-making implies a conversation, which is one of the reasons I love it. It's not a monologue. It's not just us listening. It's a back and forth until you know, we figure each other out. Beatrice Preti: Yes. Mikkael Sekeres: I wonder if I could ask you one more question. In your essay, you ask the question, "Do we struggle with moral distress when a patient makes a choice that we disagree with based on values that we ourselves do not hold?" Do you think you can answer your own question? Beatrice Preti: So this is getting to my academic work, and my PhD work that we spoke a little bit about in the beginning. I think it's something that we need to be mindful of. Certainly in my training, certainly when I was less experienced, there would be a lot of moral distress because we are not all clones of each other. We are people, but we have our own beliefs, we have our own backgrounds, we have our own experiences. There are times when people, and not just in medicine, but certainly in medicine, certainly patients make decisions that I don't quite understand because they are so different from what I would make or what I would choose for myself or for a family member. On the flip side, I think I've gotten myself, and I've had enough experience at this point in my career, to be able to separate that and say, you know, “But this is someone who has clearly thought things through and based on their own world view, their own perspectives, their own life experiences, this is the choice that's best for them.” And that's certainly something that I can support and I can work with a patient on. But it takes time, right? And it takes very deliberate thought, a lot of mindfulness, a lot of practice to be able to get to that point. Mikkael Sekeres: Well, I think that's a beautiful point to leave off with here. We've been talking to Beatrice Preti, who is an assistant professor at Emory University and an adjunct professor at Western University, and a PhD candidate with Maastricht University to discuss her JCO Oncology Practice article, "No Versus Know: Patient Empowerment Through Shared Decision-Making." Beatrice, thank you so much for joining me today. Beatrice Preti: Absolutely. Mikkael Sekeres: If you've enjoyed this episode, consider sharing it with a friend or a colleague or leave us a review. Your feedback and support helps us continue to have these important conversations. If you're looking for more episodes and context, follow our show on Apple, Spotify, or wherever you listen, and explore more from ASCO at asco.org/podcasts. Until next time, this has been Mikkael Sekeres for JCO Cancer Stories: The Art of Oncology. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show Notes: Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr Beatrice Preti is an Assistant Professor at Emory University Additional Material: Knuckleheads, by Dr Timothy Gilligan and accompanied podcast episode.

Racial and Ethnic Disparities Among Medicare Beneficiaries

Play Episode Listen Later Aug 28, 2025 28:43

Host Davide Soldato and guest Dr. John K. Lin discuss the JCO article "Racial and Ethnic Disparities Along the Treatment Cascade Among Medicare Fee-For-Service Beneficiaries with Metastatic Breast, Colorectal, Lung, and Prostate Cancer." TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Davide Soldato: Hello, and welcome to JCO After Hours, the podcast where we sit down with authors of the latest articles published in the Journal of Clinical Oncology. I'm your host, Dr. Davide Soldato, a medical oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by Dr. Lin, assistant professor in the Department of Health Services Research at the University of Texas MD Anderson Cancer Center. Dr. Lin and I will be discussing the article titled, "Racial and Ethnic Disparities Along the Treatment Cascade Among Medicare Fee-for-Service Beneficiaries With Metastatic Breast, Colorectal, Lung, and Prostate Cancer." Thank you for speaking with us, Dr. Lin. Dr. Lin: Thank you so much for having me. I appreciate it. Dr. Davide Soldato: So, just to start, to frame a little bit the study, I just wanted to ask you what prompted you and your team to look specifically at this question - so, racial and ethnic disparities within this specific population? And related to this question, I just wanted to ask how this work is different or builds on previous work that has been done on this research topic. Dr. Lin: Yeah, absolutely. Part of the impetus for this study was the observation that despite people who are black or Hispanic having equivalent health insurance status - they all have Medicare Fee-for-Service - we've known that treatment and survival differences and disparities have persisted over time for patients with metastatic breast, colorectal, lung, and prostate cancer. And so, the question that we had was, "Why is this happening, and what can we do about it?" One of the reasons why eliminating racial and ethnic disparities in survival among Medicare beneficiaries with metastatic cancer has been elusive is because these disparities are occurring along a lot of dimensions. Whether or not it's because the patient presented late and has very extensive metastatic cancer; whether or not the patient has had a difficult time even seeing an oncologist; whether or not the patient has had a difficult time starting on any systemic therapy; or maybe it's because the patient has had a difficult time getting guideline-concordant systemic therapy because, more recently, these treatments have become so expensive. Disparities, we know, are occurring along all of these different facets and areas of the treatment cascade. Understanding which one of these is the most important is the key to helping us alleviate these disparities. And so, one of our goals was to evaluate disparities along the entire treatment cascade to try to identify which disparities are most important. Dr. Davide Soldato: Thank you very much. That was very clear. So, basically, one of the most important parts of the research that you have performed is really focusing on the entire treatment cascade. So, basically, starting from the moment of diagnosis up to the moment where there was the first line of treatment, if this line of treatment was given to the patient. So, I was wondering a little bit, because for this type of analysis, you used the SEER-Medicare linked database. So, can you tell us a little bit which was the period of time that you selected for the analysis? Why do you think that that was the most appropriate time to look at this specific question? And whether you feel like there is any potential limitation in using this type of database and how you handled this type of limitations? Dr. Lin: Yeah, absolutely. It's a great question. And I want to back up a little bit because I want to talk about the entire treatment cascade because I think that this is really important for our research and for future research. We weren't the first people to look at along the treatment cascade for a disease. Actually, this idea of looking along the treatment cascade was pioneered by HIV researchers and has been used for over a decade by people who study HIV. And there are a lot of parallels between HIV and cancer. One of them is that with HIV, there are so many areas along that entire treatment cascade that have to go right for somebody's treatment to go well. Patients have to be diagnosed early, they have to be given the right type of antiretrovirals, they have to be adherent to those antiretrovirals. And if you have a breakdown in any one of those areas, you're going to have disparities in care for these HIV patients. And so, HIV researchers have known this for a long time, and this has been a big cornerstone in the success of getting people with HIV the treatment that they need. And I think that this has a lot of parallels with cancer as well. And so, I am hoping that this study can serve as a model for future research to look along the entire treatment cascade for cancer because cancer is, similarly, one of these areas that requires multidisciplinary, complex medical care. And understanding where it is breaking down, I think, is crucial to us figuring out how we can reduce disparities. But for your question about the SEER-Medicare linked database, so we looked between 2016 and 2019. That was the most recent data that was available to us. And one of the reasons why we were excited to look at this is because there were some new treatments that were just released and FDA-approved around 2018, which we were able to study. And this included immunotherapy for non–small cell lung cancer, and then it also included androgen receptor pathway inhibitors, the second-generation ones, for prostate cancer. And the reason why this is important is because for some time, as we have developed these new therapies, there's been a lot of concern that there have been disparities in access to these novel therapies because of how expensive they are, particularly for the Medicare population. And so one of the reasons why we looked specifically at this time period was to understand whether or not, in more recent years, these novel therapies, people are having increasing disparities in them and whether or not increasing disparities in these more expensive, newer therapies is contributing to disparities in mortality. That being said, obviously, we're in 2025 and these data are by now six years old, and so there are additional therapies that are now available that weren't available in the past. But I think that, that being said, at least it's sort of a starting point for some of the more important therapies that have been introduced, at least for non–small cell lung cancer and prostate cancer. And the database, SEER-Medicare, is helpful because it uses the population cancer registry, which is the SEER registry cancer registry, linked to Medicare claims. So, any type of medical care that's billed through Medicare, which is going to basically be all of the medical care that these patients receive, for the most part, we're going to be able to see it. And so, I think that this is a really powerful database which has been used in a lot of research to understand what kind of care is being received that has been billed through Medicare. So, one of the limitations with this database is if there is care that's received that was not billed through Medicare, we're not going to be able to see that. And this does not happen probably that frequently, particularly because most patients who have insurance are going to be receiving care through insurance. However, we may see it for some of the oral Part D drugs. Some of those drugs are so expensive that patients cannot pay for the coinsurance during that time. And it's possible that some of those drugs patients were getting for free through the manufacturer. We potentially missed some of that. Dr. Davide Soldato: So, going a little bit into the results, I think that these are very, very interesting. And probably the most striking one is that when we look at the receipt of any type of treatment for metastatic breast, colorectal, prostate, and lung cancer - and specifically when we look at guideline-directed first-line treatments - you observed striking differences. So, I just wanted you to guide us a little bit through the results and tell us a little bit which of the numbers surprised you the most. Dr. Lin: So, what we were expecting is to see large disparities in receiving what we called guideline-directed systemic therapy. And guideline-directed systemic therapy during this time kind of depended on the cancer. So, we thought that we were going to see large disparities in guideline-directed therapy because these were the more novel therapies that were approved, and thus they were going to be the more expensive therapies. And so, what this meant was for colorectal cancer, this was going to be any 5-FU–based therapy. For lung cancer, this was going to be any checkpoint inhibitor–based therapy. For prostate cancer, this was going to be any ARPI, so this was going to be things like abiraterone or enzalutamide. And for breast cancer, this was going to be CDK4 and 6 TKIs plus any aromatase inhibitor. And so, for instance, for breast, prostate, and lung cancer, these were going to be including more expensive therapies. And so, what we expected to see was large disparities in receiving some of these more expensive, novel therapies. And we thought we were going to see fewer disparities in receiving some of the cheaper therapies, such as aromatase inhibitors, 5-FU, older platinum chemotherapies for lung cancer, and ADT for prostate cancer. We were shocked to find that we saw large racial and ethnic disparities in seeing some of the older, cheaper chemotherapies and hormonal therapies. So for instance, for breast cancer, 59% of black patients received systemic therapy, whereas 68% of white patients received systemic therapy. For colorectal, only 23% of black patients received any systemic therapy versus 34% of white patients. For lung, only 26% of black patients received any therapy, whereas 39% of white patients did. And for prostate, only 56% of black patients received any systemic therapy versus 77% of white patients. And so, we were pretty shocked by how large the disparities were in receiving these cheap, easy-to-access systemic therapies. Dr. Davide Soldato: Thank you very much. So, I just wanted to go a little bit deeper in the results because, as you said, there were striking differences even when we looked at very old and also cheap treatments that, for the majority of the patients that were included inside of your study, were actually basically available for a very small price to these patients who had the eligibility for Medicare or Medicaid. And I think that one of the very interesting parts of the research was actually the attention that you had at looking how much of these disparities could be explained by several factors. And actually, one of the most interesting results is that you observed that low-income subsidy status was actually a big determinant of these disparities in terms of treatment. So, I just wanted to guide us a little bit through these results and then just your opinion about how these results should be interpreted by policymakers. Dr. Lin: Yeah, absolutely. I'm going to explain a little bit about what low-income subsidy status is and dual-eligibility status. Some of the listeners may not know what low-income subsidy status or dual-eligibility status is. Low-income subsidy status is part of Medicare Part D. Medicare Part D is an insurance benefit that allows patients to receive oral drugs. So these are drugs that are dispensed through the pharmacy, such as the CDK4/6 inhibitors, as well as second-generation ARPIs in our study. For patients who have Medicare Part D and whose income is low enough - falls below a certain federal poverty level threshold - those patients will receive their oral drugs for much cheaper. And this is really important for some of these more novel therapies because for some of these more novel therapies, if you don't have low-income subsidy status, you may be paying thousands of dollars for a single prescription of those drugs. Whereas if you have low-income subsidy status, you may be paying less than $10. And so that difference, greater than $1,000 or $2,000 versus less than $10, one would think that the patient who's paying less than $10 would be much more likely to receive those therapies. So that's low-income subsidy status. Low-income subsidy status, importantly, doesn't apply for infused medications like immunotherapy. But it's important to know that most people with low-income subsidy status - about 88% - are also dual-eligible. What dual-eligible means is that they have both Medicare and Medicaid. Medicare being the insurance that everybody has in our study who's greater than 65. And Medicaid is the state-run but federally subsidized insurance that patients with low incomes have. And so patients who are dual-eligible - and about 87% of those with low-income subsidy status are dual-eligible - those patients have both Medicaid and Medicare, and they basically pay next to nothing for any of their medical care. And that's because Medicare will reimburse most of the medical care and the copays or coinsurance are going to be covered by Medicaid. So Medicaid is going to pick up the rest of the bill. So, most of the patients who have low-income subsidy status who are dual-eligible, these patients pay almost nothing for their medical care - Part B or Part D, any of their drugs. And so, one would expect that if cost were the main determinant of disparities in cancer care, then one would expect that dual-eligibles, most of them would be receiving treatment because they're facing minimal to no costs. What we found is that when we broke down the racial and ethnic disparity by a number of factors - including LIS status/dual eligibility, age, the number of comorbidities, etcetera - what we found was that the LIS or dual-eligibility status explained about 20% to 45% of the disparities that we saw in receiving treatment. And what that means is despite these patients paying next to nothing for their drugs, these are the most likely patients to not be treated for their cancer at all. So they're most likely to basically be diagnosed, survive for two months, see an oncologist, and then never receive any systemic therapy for their cancer. And this is not just chemotherapies for colorectal or lung cancer. This includes cheaper, easier-to-tolerate hormonal therapies that you can just take at home for breast cancer, or you can get every six months for prostate cancer, that people who even have poorer functional status are able to take. However, for whatever reason, these dual-eligible or LIS patients are very unlikely to receive treatment compared to any other patient. The low likelihood of treating this group of patients, that explains a large portion of the racial and ethnic disparities that we see. Dr. Davide Soldato: And one thing that I think is very interesting and might be of potential interest to our listeners is, did you compare survival outcomes in these different settings? And did you observe any significant differences in terms of racial and ethnic disparities once you saw that there was a significant difference when looking at both receipt of any type of treatment and also guideline-directed treatments? Dr. Lin: We saw that there were large disparities in survival by race and ethnicity when you look overall. However, when you just account for the patients who received any systemic therapy at all - not just guideline-directed systemic therapy - those differences in survival essentially disappeared. And so, what that suggests is that if black patients were just as likely to receive any systemic therapy at all as white patients, we would expect that the survival differences that we were seeing would disappear. And this is not even just looking at guideline-directed systemic therapy. This was looking just at systemic therapy alone. And so, while guideline-directed systemic therapy should be a goal, our research suggests that if we are to close the gap in disparities in overall survival among black and white patients, we must first focus on patients just receiving any type of treatment at all. And that should be the very first focus that policymakers, that leaders in ASCO, that health system leaders, that physicians, that we should focus on: just trying to get any type of treatment to our patients who are poorer or black. Dr. Davide Soldato: Thank you very much. And this was not directly related to the research that you performed, but going back to this very point - so, increasing the number of patients that receive any kind of systemic treatment before looking at guideline-directed treatments - what would you feel would be the best way to approach this in order to decrease the disparities? Would you look at interventions such as financial navigation or maybe improving referral pathways or providing maybe more culturally adapted information to the patients? Because in the end, what we see is disparities based on racial and ethnicity. We see that we can reduce these disparities if we get these patients to the treatment. But in the end, what would you feel is the best way to bring patients to these types of treatments? Dr. Lin: I think the most important thing is to understand that these disparities are not primarily happening because of the high cost of cancer treatment. These disparities are happening because of other social vulnerabilities that these patients are facing. And so these vulnerabilities could be a lot of things. It could be mistrust of the medical system. It could be fear of chemotherapy or other treatments. It could be difficulty taking time off of work. It could be any number of things. What we do know is when we've looked at the types of interventions that can help patients receive treatment, navigation is probably the most effective one. And the reason why I think that is because when patients don't receive treatment because of social vulnerability, I sort of look at social vulnerability like links in a chain. Any weakest link is going to result in the patient not receiving treatment. This may be because they have a hard time taking time off of work. This may be because they had a hard time getting transportation to their physician. It may be because they had an interaction with a physician, but that interaction was challenging for the patient. Maybe they mistrusted the physician. Maybe they're worried about the medical system. If any of these things goes wrong, the patient is not going to be treated. The patient navigator is the only person who can spot any of those weak links within the chain and address them. And so, I think that the first thing to do is to get patient navigation systems in place for our vulnerable patients throughout the United States. And this is incredibly important because in Medicare, patient navigation is reimbursable. And so this is not something that's ‘pie in the sky'. This is something that's achievable today. The second thing is that it's really important that we see these vulnerabilities happening for patients who are dual-eligible, who have both Medicare and Medicaid. One of the reasons why this is important is because there has been a lot of research outside of what we've done that has shown vulnerabilities for dual-eligible patients who have Medicare for a number of different diseases. And the reason why is because, although patients are supposed to have the benefits of both Medicare and Medicaid, usually these two insurances do not play nicely together. It creates a huge, bureaucratic, complex mess and maze that most of these patients are unable to navigate. And so many of these patients are unable to actually receive the full reimbursement from both Medicare and Medicaid that they should be getting because those two insurers are not communicating well. And so the second thing is that national cancer organizations need to be supporting policies and legislation that is already being discussed in Congress to revamp the dual-eligible system so that it facilitates these patients getting properly reimbursed for their care from both Medicare and Medicaid and these systems working together well. The third thing is that Medicaid itself has many benefits that can allow patients to receive care, like they have transportation benefits so that patients can get to and from their doctor's appointments with ease. And so I think this will be additionally very, very helpful for patients. The last thing is, you know, it's possible that future innovations such as telemedicine and tele-oncology and cancer care at home can also make it easier for some of these patients who may be working a lot to receive care. But what I would say is that our study should be a call for healthcare delivery researchers to start piloting interventions to be able to help these patients receive systemic therapy. And so what this could look like is trying to get that care navigation and implement that in clinics so that patients can be receiving the care that they need. Dr. Davide Soldato: Thank you very much. That was a very clear perspective on how we can tackle this issue. So, I just wanted to close with a sort of personal question. I was wondering what led you to work specifically in this research field that is very challenging, but I think it's particularly critical in healthcare systems like in the United States. Dr. Lin: Yeah, absolutely. One of the most important things for me as an oncologist and a researcher is being able to know that all patients in the United States - and obviously abroad - who have cancer should be able to receive the kind of care that they deserve. I don't think that patients, because their incomes are lower or because their skin looks a certain color or because they live in rural areas, these shouldn't be determinants of whether or not cancer patients are receiving the care that they need. We can develop and pioneer the very best treatments and breakthroughs in oncology, but if our patients are not receiving them - if only 20% of our patients with colon cancer or lung cancer are receiving any type of systemic therapy, who are black - this is a big problem. But this is something that I think that our system can tackle. We need to get these breakthroughs that we have in oncology to every single cancer patient in America and every single cancer patient in the world. I think this is a goal that all oncologists should have, and I think that this is something that, honestly, is achievable. I think that research is a powerful tool to give us a lens into understanding exactly why it is that certain patients are not getting the care that they deserve. And my goal is to continue to use research to shed light on why our system is not performing the way that we all want it to be. Dr. Davide Soldato: Circling back to your research, actually the manuscript that was published was supported by a Young Investigator Award by the American Society of Clinical Oncology. So, was this the first step of a more broad research, or do you have any further plans to go deeper in this topic? Dr. Lin: Yeah, absolutely. First, I want to thank the ASCO Young Investigator Award for funding this research because I think it's fair to say that this research would not have happened at all without the support of the ASCO YIA. And the fact that ASCO is doing as much as it can to support the future generation of cancer researchers is incredible. And it's a huge resource, and having it come at the time that it did is critical for so many of us. So I think that this is an unbelievable thing that ASCO does and continues to do with all of its partners. For me, yeah, this is definitely a stepping stone to further research. Medicare Fee-for-Service is only one part of the population. I want to spread this research and extend it to patients who have other types of insurances, look at other types of policies, and also try to conduct some of the cancer care delivery research that's needed to try to pilot some interventions that can resolve this problem. So hopefully this is the first step in a broader series of studies that we can all do collectively to try to eliminate racial and ethnic disparities in cancer care and survival. Dr. Davide Soldato: So, I think that we've come at the end of this podcast. Thank you again, Dr. Lin, for joining us today. Dr. Lin: Thank you so much. It was a pleasure to be a part of this. Dr. Davide Soldato: So, we appreciate you sharing more on your JCO article, "Racial and Ethnic Disparities Along the Treatment Cascade Among Medicare Fee-for-Service Beneficiaries With Metastatic Breast, Colorectal, Lung, and Prostate Cancer." If you enjoy our show, please leave us a rating and review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

JCO Article Insights: Lymph Node Dissection for Lung Cancer

Play Episode Listen Later Aug 25, 2025 21:49

In this JCO Article Insights episode, Dr. Joseph Matthew interviews authors Dr. Yang Zhang and Dr. Haiquan Chen about their recently published JCO article, "Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity–Dominant Lung Adenocarcinoma" TRANSCRIPT Joseph Mathew: Welcome to the Journal of Clinical Oncology Article Insights episode for the August issue of the JCO. This is Joseph Mathew, editorial fellow for JCO, and today, it is my pleasure to have with us Dr. Haiquan Chen and Dr. Yang Zhang, authors of the recently published manuscript, "Phase 3 Study of Mediastinal Lymph Node Dissection for Ground-Glass Opacity-Dominant Lung Adenocarcinoma," which we will be discussing today. Dr. Chen is the Director of the Institute of Thoracic Oncology at Fudan University and the Chief of Thoracic Surgery at Fudan University Shanghai Cancer Center, where he is also the Head of Thoracic Oncology MDT and the Director of the Lung Cancer Center. Dr. Chen is a surgeon-scientist and a pioneer in developing individualized surgical strategies for early-stage non-small cell lung cancer. Dr. Zhang is a surgical oncologist and a member of the team which Dr. Chen leads at the Fudan University Shanghai Cancer Center. Welcome Dr. Chen and Dr. Zhang. Thank you very much for accepting our invitation and joining us today as part of this podcast episode. To summarize the salient points, this study presented the interim analysis of a multi-center, open-label, non-inferiority, randomized controlled trial investigating the necessity of systematic mediastinal lymph node dissection at the time of segmentectomy or lobectomy in patients with clinical stage T1N0M0 ground-glass opacity-dominant invasive lung adenocarcinoma, as defined by a consolidation-to-tumor ratio of 0.5 or less on thin-section computed tomography and a maximum tumor diameter of 3 cm or less. Eligible participants with intraoperatively confirmed invasive adenocarcinoma on frozen section analysis were randomized to either the systematic mediastinal lymph node dissection arm or to no mediastinal lymph node dissection. In the latter experimental group, mediastinal lymph nodes comprising the N2 nodal stations were not dissected, and the hilar nodes were variably addressed at the discretion of the operating surgeon. The primary endpoint of the trial was disease-free survival at 3 years. Secondary endpoints included perioperative outcomes, the status of lymph node metastasis in the systemic lymph node dissection arm, and 3-year overall survival. Before the trial reached its accrual target, a pre-planned interim safety analysis set for the time point when enrollment reached 300 patients was performed. It was noted that while none of the patients in either arm had nodal metastasis on postoperative pathological evaluation, lymph node dissection-related intraoperative and postoperative complications were more commonly observed in the systematic lymph node dissection arm, including one life-threatening episode of massive bleeding. Since this met the predefined criteria for trial termination, and in accordance with the principle of non-maleficence, further recruitment was stopped and the trial terminated. Although the 3-year disease-free survival and the overall survival for the enrolled patients were comparable, operative outcomes, including the duration of surgery, blood loss, chest tube duration, length of postoperative stay, and the rate of clinically significant complications, were significantly lower in the experimental arm compared with the systematic lymph node dissection group. The authors concluded that for well-selected patients, mediastinal nodal dissection could be omitted without adversely affecting oncological outcomes, representing a significant shift in current surgical practice, given that guidelines the world over recommend systematic lymph node dissection or sampling for all invasive lung cancers. In summary, this study addressed a clinically relevant question with regard to the extent of nodal dissection, especially in the light of recent evidence recommending less extensive parenchymal dissections for early-stage non-small cell lung cancer, with the findings suggesting that invasive lung adenocarcinoma associated with ground-glass opacities of consolidation-to-tumor ratio up to 0.5 was an excellent predictor of tumor biology, and in clinical T1N0M0 lesions, a reliable predictor of negative mediastinal lymph node involvement. So Dr. Chen and Dr. Zhang, could you tell us some more about what led you to do this research and the challenges which you faced while recruiting patients for this trial? Dr. Yang Zhang: Dr. Mathew, thank you for your summary. The current clinical guidelines recommend systematic lymph node dissection or sampling for every patient with early-stage lung cancer, regardless of their lymph node status. And in our clinical practice, we observe that this procedure causes a lot of surgical complications including chylothorax and recurrent laryngeal nerve injury. Furthermore, dissecting the tumor-draining lymph nodes actually may potentially damage the body's anti-tumor immunity. So, Dr. Chen proposed the concept of selective lymph node dissection, which we aimed to dissect the metastatic lymph nodes, while at the same time we try to preserve as many uninvolved lymph nodes as possible. So previously, we have conducted a series of retrospective studies to identify reliable predictors of nodal negative status in certain mediastinal zones, and we have performed a prospective observational phase 2 clinical trial to validate that the six criteria we proposed are 100% in predicting node-negative status. And this forms the basis for our phase 3 clinical trial. Dr. Haiquan Chen: This trial is only one of the series of trials. The meaning of this trial you already said. And for a long time, from the surgeon's point of view, we considered minimally invasive surgery. It minimizes the size of the incision and minimizes the number of the holes we made. So, the true and the high-impact of minimally invasive, we make a concept of minimal dissection, that means organ-level minimally invasive. So we proposed the concept of minimally invasive 3.0, that means minimal incision, minimal dissection (that means organ-level minimal), and systemic minimally invasive. So at first, we judged from the point of minimally invasive surgery. As long as immunotherapy is widely used in the clinical practice, we know immunotherapy, that means you use drugs to stimulate and activate the lymph node site. If we dissect all the metastatic lymph nodes, cut them out, how can we restimulate that lymph node site? So, from minimally invasive trauma and second, from the functional aspect, to try to save as many uninvolved lymph nodes as possible. Joseph Mathew: Thank you, Dr. Chen. That's a very interesting concept that you alluded to even in the discussion of this paper, as to the potential role of the non-metastatic lymph nodes as immune reservoirs. So, coming back to this paper, were there any challenges which you faced while recruiting patients for this trial? Dr. Haiquan Chen: The criteria is very clear. That means invasive adenocarcinoma, that means most of the centimeter is 3.0 centimeter and also CTR ratio less than 0.5. And we can see that, you know, we did study about that. Even the invasive component of the subsolid nodule, it's bigger than the solid part. That means even the pure GGO, we can find out that there's still some invasive component. From this point of view, pure GGO and subsolid GGO, from this part of invasive carcinoma, that means it's a special clinical subtype that we, from retrospective study and also prospective study, we find out this group of patients, there are no mediastinal lymph node metastasis. So I think it's very important for this kind of group that we can avoid doing the mediastinal lymph node dissection. And we can do organ-level minimally invasive surgery. And also, we try to keep the patient's immune function as normal as possible. Dr. Yang Zhang: Well, Dr. Mathew, we believe that the biggest challenge when we are enrolling these patients is that there needs to be a paradigm shift in the mind because systematic lymph node dissection has long been the standard of care. And some patients may misunderstand. Before the enrollment, we have to give them informed consent, but if the patient hears that they may be enrolled in the no-lymph-node-dissection group, they may feel that they do not receive radical, curative-intent surgery. So we believe, as Dr. Chen has said, after the release of our results, the no-lymph-node dissection may be incorporated in the future guideline for those patients without lymph node involvement, we can just omit the lymph node dissection. Joseph Mathew: The study described two pre-planned interim points during the course of subject enrollment when the data was analyzed. So Dr. Chen and Dr. Zhang, could you please explain a little more about these two interim points of analysis that were planned and the rationale behind it? Dr. Yang Zhang: When conducting this trial, we have two concerns. One is if there is any lymph node metastasis, there may be omission of metastatic lymph nodes not dissected in the no-lymph-node-dissection group. And there is another concern is that if all these lymph nodes are uninvolved, then dissecting these lymph nodes may cause life-threatening complications. So, we set the 150 interim analysis to ensure that there is no lymph node involvement in this group. And the other early termination criteria is set because if there is no lymph node involvement found in both groups, then a severe complication which is life-threatening is unacceptable because it threatens the patient's safety. Joseph Mathew: So, although you did briefly allude to in the paper, what was the basis for selecting DFS as the primary endpoint when the objective of this trial was to assess nodal involvement in this subset of tumors? Dr. Yang Zhang: Well, previously, we have done a series of retrospective studies and one prospective phase 2 trial. And in these studies, we have identified that GGO-dominant lung adenocarcinoma, even if it's invasive, it has no lymph node involvement. So this phase 3 trial was primarily designed to compare the survival outcomes. But as the trial went on, as Dr. Chen has concerns that if the patients have no lymph node metastasis at all, it may be unfair to dissect the lymph nodes for patients enrolled in the systematic lymph node dissection group. So there is one life-threatening complication that happens due to dissecting the lymph nodes and injury to the superior vena cava, which leads to massive bleeding. It is at this point that we decided to terminate this trial for patient safety concerns. Joseph Mathew: Yeah, that's a very fair point. So you made sure that the ethical considerations were kept intact. So another point was, there was a mention in the study of the historical data from your institution suggesting a 3-year disease-free survival of 96.6% for patients with clinical T1N0M0 ground-glass opacity-dominant invasive lung adenocarcinoma. So could you please elaborate on the patterns of recurrence which you noted for this group of patients who had developed a recurrence? Dr. Haiquan Chen: Yeah, I think over 90% 3-year DFS, that's the least. From our retrospective data for this kind of group of patients, their DFS is so good. To the best of my knowledge, almost 100%. So this is very conservative, 94, 90% is very conservative. I think the trial eventually would have been positive. It's a special clinical subtype, even for invasive adenocarcinoma, their prognosis is much better than the other type of invasive adenocarcinoma. Joseph Mathew: So this question may be slightly outside the purview of this study, but in your clinical practice, would you advocate either segmentectomy or lobectomy for all patients meeting the trial criteria, that is, lesions measuring 3 cm or less with a CTR of up to 0.5? Or is there a subgroup of patients you would recommend a wedge dissection for? Dr. Haiquan Chen: I think CTR ratio is one parameter and also the location is another very important parameter. So we put it together to make a decision, the patient should do a lobectomy or segmentectomy. Even for an ongoing trial, for even the patient, invasive adenocarcinoma, we can do in the right location, even wedge, it can achieve enough negative margin in the ongoing trial to verify the comparable result for the patient, we can do the wedge dissection. So not just the CTR ratio, that's not the only parameter to make a decision on what kind of procedure we'll do. Joseph Mathew: Yeah, great point, Dr. Chen. So from my perspective, this study was a well-designed, randomized control trial based on a relevant and clinically valid research question. So what, in your opinion, are the main strong points of this study? Dr. Yang Zhang: We believe that this study represents the first randomized clinical trial published, yet, regarding the topic of selective lymph node dissection. It basically offers the highest level of evidence. We believe our results should be incorporated in the future clinical guideline. Joseph Mathew: Given the increasing incidence of these lesions, I think it was- a randomized control trial in this arena was much awaited. And the other point is that GGO-dominant lung adenocarcinomas, the specific clinical guidelines are not very clear. So I think your study brought out that lymph node dissection for these tumors which satisfy the eligibility criteria could be omitted safely. Important consideration here is that the conclusions of the trial were based on an interim analysis, and this analysis was not planned for an early assessment of the primary endpoint. In other words, the study was not adequately powered to detect a significant difference in DFS at 3 years. So Dr. Chen and Dr. Zhang, what do you perceive are the most important limitations of this study which you feel should be addressed in future research? Dr. Haiquan Chen: So the surgery now is more individualized. I think the surgery from the last two decades, from the maximum tolerable intervention to minimum effective treatment, there's a big shift. So I think that the consensus, we can preserve normal lung parenchyma as much as possible. For the lymph nodes, I think that the big shift, we should shift it to keep as many as uninvolved lymph nodes as possible. So that's very important, not just to reduce the intraoperative trauma, but also to keep the immune environment as normal as possible. Joseph Mathew: Another point was the limited long-term follow-up data to determine the actual impact of omitting lymph node dissection on local-regional disease control. So is any future follow-up planned to assess the long-term survival outcomes for the 302 patients which were enrolled in this trial? Dr. Haiquan Chen: Yeah, I think that's very important for us. This trial we terminated just because if we keep the trial going, it's unfair for the mediastinal lymph node dissection group. We tried to just stop here, and we shifted to the single-arm trial. So, 2 or 3 years, this trial and another trial, they will give our final result to demonstrate more if selective mediastinal lymph nodes have a better result than ever before. And we will support the mediastinal lymph node dissection. That's one way. And the American College just asked me, how can we put this policy into clinical practice in the United States? Because most of the patients they meet have solid tumors. So we have another trial, try to figure out how we can make sure before and intraoperative the lymph node status is negative or positive, and then we can solve that problem and put this policy into clinical practice in the Western society. Joseph Mathew: Great. So that would be something we should all be looking forward to. So, this brings me to the final point of discussion on future research in this field. Dr. Chen, you commented in the paper that future studies should focus on improving the reproducibility of CTR evaluation. What are your thoughts on this subject? Dr. Haiquan Chen: The CTR ratio, the concept from the JCOG 0201, just a concept from that prospective study, the phase 2 study, only subgroup analysis they give the concept of CTR ratio and the diameter. How can we reproduce? In our group and also I believe in Japan and in China, in Korea, and in our daily practice, I think CTR ratio is not a big issue. There are two very important things. One, you make sure the CTR ratio, not in a common CAT scan, but in a high-resolution CAT scan. So the imaging, that's the first thing. And the second, not from the single section and a two or three section, you make sure that your calculation is accurate. That's not just the single section, you make sure that you got the conclusion, the CTR ratio is the same number. We make sure that totally we, from the top to the bottom of the whole lesion, we make sure that the CTR ratio is accurate. Joseph Mathew: Thank you, Dr. Chen. I think that would involve training our radiologists also to be aware of the CTR ratio and how it should be interpreted. So another very interesting concept which you had alluded to in the discussion was the potential role of non-metastatic lymph nodes as immune reservoirs. So how do you think we could preserve these nodes and do you think sentinel node biopsies would play a role in future? Dr. Yang Zhang: Actually, Dr. Chen has also led some basic research on this topic. We are investigating the immunological role of the tumor-draining lymph nodes. And our preliminary results have already shown that the tumor-draining lymph nodes of lung cancer, especially those uninvolved lymph nodes, have a vital role in the anti-tumor immunity and also effective response to the current anti-PD-1 immunotherapy. In the future, we believe that by incorporating our clinical evidence and those findings from our basic research, we will be able to provide very strong rationale to support selective lymph node dissection. Joseph Mathew: So lastly, what are the questions that still remain to be answered and what do you perceive as the next step in this field? Dr. Haiquan Chen: I think for the lung cancer surgery, especially for the cT1N0M0, they are more individualized. We can, based on the patient, the location, the CTR ratio, we can do wedge dissection, or segmentectomy, or lobectomy. For the lymph node dissection, we can do no mediastinal lymph node dissection or selective, only to dissect the positive one, or we have to do the systemic mediastinal lymph node dissection. So we can see there are too many combinations. So in the near future, for the surgery perspective, we have it more individualized. In the future, we just try to make sure we do not cut as many as possible. We just make sure that we can avoid over-diagnosis or overtreatment or over-dissected. I think that in the near future, that goal will come true. Joseph Mathew: That's a great point, Dr. Chen. So that would be something also for the thoracic oncology community to work towards. This wraps up today's episode of JCO Article Insights. Dr. Chen and Dr. Zhang, thank you very much for taking the time to join us today in what has been a very insightful session. Dr. Haiquan Chen: Thank you. Dr. Yang Zhang: Thanks. Joseph Mathew: To our audience, thank you for listening. Please stay tuned for more interviews and articles, summaries, and be sure to leave us your comments and ratings. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Venetoclax Dosing & APOLLO

Oncology Peer Review On-The-Go

Play Episode Listen Later Aug 21, 2025 17:47

Malignant Hematology Updates: Venetoclax dosing strategies continue to evolve HMA/Ven + IDH1/2 inhibitors: https://doi.org/10.1200/JCO-25-00640 HMA/Ven + revumenib: https://doi.org/10.1200/JCO-25-00914 Venetoclax + CPX-351: https://doi.org/10.1002/ajh.27723 APOLLO: https://doi.org/10.1200/JCO-25-00535 Iland APOLLO editorial: https://doi.org/10.1200/JCO-25-01496 ctDNA assessment vs. PET in Large B-Cell Lymphoma: https://doi.org/10.1200/JCO-25-01534

apollo dosing jco

S1 Ep173: Integrating Dato-DXd Into Early-Line EGFR-Mutant NSCLC Management

Play Episode Listen Later Aug 4, 2025 23:31

In a discussion with CancerNetwork®, Jacob Sands, MD, assistant professor of Medicine at Harvard Medical School, thoracic oncologist at the Dana-Farber Cancer Institute, and investigator of the phase 2 TROPION-Lung05 trial (NCT04484142) and phase 3 TROPION-Lung01 trial (NCT04656652), which supported the accelerated approval of datopotamab deruxtecan-dlnk (dato-DXd; Datroway) in pretreated EGFR-mutant metastatic NSCLC in June 2025, discussed safety and efficacy considerations for the agent's use.1-3 He began by outlining a combined cohort of the TROPION-Lung05 and TROPION-Lung01 trials, which collectively showed an efficacy benefit with dato-DXd in patients with EGFR-mutant disease vs docetaxel. In the combined cohort, the median progression-free survival with dato-DXd reached 5.8 months, and the median overall survival was 15.6 months. Additional efficacy data revealed an objective response rate of 45% (95% CI, 35%-54%) and a median duration of response of 6.5 months (95% CI, 4.2-8.4). Furthermore, Sands highlighted the most common toxicities observed with dato-DXd in this population, which included stomatitis, interstitial lung disease (ILD), and ocular toxicities. He also reviewed management strategies to mitigate their incidence and severity. Specifically, remedies include prophylaxis, oral hygiene, and dose reductions for stomatitis; using preservative-free eye drops and ophthalmology visits for ocular toxicity management and prevention; and monitoring for any incidence of high-grade ILD. He then touched upon next steps for research in this disease state, including the phase 2 ORCHARD trial (NCT03944772) evaluating dato-DXd with osimertinib (Tagrisso) in the second-line setting after progression on osimertinib and the phase 3 TROPION-Lung15 trial (NCT06417814), which is evaluating chemotherapy vs dato-DXd alone or with osimertinib.4,5 Sands concluded by discussing the implications for toxicity management in patients who experience responses that exceed median outcomes, suggesting that the toxicity profile may be more severe for this group. Emphasizing the broadness of outcomes with any drug, he expressed that patients with experiences that deviate from the observed median outcome are an important consideration for clinical practice. References Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. Published online January 6, 2025. doi:10.1200/JCO-24-01349 Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol. Published online September 9, 2024. doi:10.1200/JCO-24-01544 FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. FDA. June 23, 2025. Accessed July 29, 2025. https://tinyurl.com/mtay7ab9 Yu HA, Goldberg SB, Le X, et al. Biomarker-directed phase II platform study in patients with EGFR sensitizing mutation-positive advanced/metastatic non-small cell lung cancer whose disease has progressed on first-line osimertinib therapy (ORCHARD). Clin Lung Cancer. 2021;22(6):601-606. doi:10.1016/j.cllc.2021.06.006 A study to investigate the efficacy and safety of dato-DXd with or without osimertinib compared with platinum based doublet chemotherapy in participants with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (TROPION-Lung15). ClinicalTrials.gov. Updated July 16, 2025. Accessed July 29, 2025. https://tinyurl.com/56z3dmsp

What Is Precision Palliative Care? Rethinking a Care Delivery Problem

ASCO Daily News

Play Episode Listen Later Jul 31, 2025 28:05

Dr. Joseph McCollom and Dr. Ramy Sedhom discuss precision palliative care, a new strategy that aims to align palliative care delivery with patient and caregiver needs instead of diagnosis alone. TRANSCRIPT ADN Podcast Episode 8-22 Transcript: What Is Precision Palliative Care? Rethinking a Care Delivery Problem Dr. Joseph McCollom: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Joseph McCollom. I'm a GI medical oncologist and palliative oncologist at the Parkview Packnett Family Cancer Institute here in Fort Wayne, Indiana. So, the early benefits of palliative care for patients with cancer have been well documented, but there are challenges in terms of bandwidth to how do we provide this care, given the workforce shortages in the oncology field. So today, we'll be exploring a new opportunity known as precision palliative care, a strategy that aims to align care delivery with patient and caregiver needs and not just diagnosis alone. Joining me for this discussion is Dr. Ramy Sedhom. He is the medical director of oncology and palliative care at Penn Medicine Princeton Health and a clinical assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine. Our full disclosures are available in the transcript of this episode. Dr. Sedhom, it's great to have you on the podcast today. Thank you so much for being here. Dr. Ramy Sedhom: Thank you, Joe. It's a pleasure to be here and lucky me to be in conversation with a colleague and friend. Yes, many of us have heard about the benefits of early palliative care. Trials have shown better quality of life, reduced symptoms, and potentially even improved survival. But as we know, the reality is translating that evidence into practice, which is really, really challenging. So Joe, both you and I know that not every patient can see palliative care, or I'd even argue should see palliative care, but that also means there are still many people with real needs who still fall through the cracks. That's why I'm really excited about today's topic, which we'll be discussing, which is precision palliative care. It's a growing shift in mindset from what's this patient's diagnosis or what's this patient's prognosis, to what matters most for this person in front of me right now and what are their individual care needs. I think, Joe, it's very exciting because the field is moving from a blanket approach to one tailored to meet people where they actually are. Dr. Joseph McCollom: Absolutely, Ramy. And I think from the early days when palliative care was kind of being introduced and trying to distinguish itself, I think one of the first models that came to clinicians' eyes was Jennifer Temel's paper in The New England Journal of Medicine in 2010. And her colleagues had really looked at early palliative care integration for patients with advanced non–small cell lung cancer. And in that era – this is a pre-immunotherapy era, very early targeted therapy era – the overall prognosis for those patients are similar to the population I serve as a GI medical oncologist, pancreatic cancer today. Typically, median overall survival of a year or less. And so, a lot of her colleagues really wanted her to track overall survival alongside quality of life and depression scores as a result of that. And it really was a landmark publication because not only did it show an improvement of quality of life, but it actually showed an improvement of overall survival. And that was really, I think, revolutionary at the time. You know, a lot of folks had talked about if this was a drug, the FDA would approve it. We all in GI oncology laugh about erlotinib, which got an FDA approval for a 2-week overall survival advantage. And so, it really kind of set the stage for a lot of us in early career who had a passion in the integration of palliative care and oncology. And I think a lot of the subsequent ASCO, NCCN, COC, Commission on Cancer, guidelines followed through with that. But I think what we realized is now we're kind of sitting center stage, there's still a lot of resource issues that if we sent a referral to palliative care for every single patient diagnosed with even an advanced cancer, we would have a significant workforce shortage issue. And so, Ramy, I was wondering if you could talk a little bit about how do we help center in on who are the right patients that are going to have the greatest benefit from a palliative care specialist intervention? Dr. Ramy Sedhom: Thanks, Joe. Great question. So you mentioned Dr. Temel's landmark 2010 trial published in the New England Journal of Medicine. And it is still a game changer in our field. The results of her work showed not only improved quality of life and mood, but I think very surprisingly at the time, a survival benefit for patients with lung cancer who had received early palliative care. That work, of course, has helped shape national guidelines, as you've shared, and it also helped define early, as within 8 weeks of diagnosis. But unfortunately, there remains a disconnect. So in clinical practice, using diagnosis or stage as the only referral trigger doesn't really match the needs that we see show up. And I think unfortunately, the other part is that approach creates a supply demand mismatch. We end up either referring more patients than palliative care teams can handle, or at the opposite extreme, we end up referring no one at all. So, I actually just wanted to quickly give, for example, two real world contrasts. So one center that I actually have friends who work in, tried as a very good quality improvement incentive, auto-refer all patients with stage IV pancreas cancer to palliative care teams. And while very well intentioned, they saw very quickly that in a two-month period, they had 30 new referrals. And on the palliative care side, there were only 15 available new patient slots. On the other hand, something that I often see in practice, is a situation where, for example, consider the case of a 90-year-old with a low-grade B-cell lymphoma. On paper, low-risk disease, but unfortunately, when you look under the microscope, this gentleman is isolated, has symptoms from his bulky adenopathy, and feels very overwhelmed by many competing illnesses. This is someone who, of course, may benefit from palliative care, but probably doesn't check the box. And I think this is where the model of precision palliative care steps in. It's not really about when was someone diagnosed or what is the prognosis or time-based criteria of their cancer, but it's really fundamentally asking the question of who needs help, what kind of help do they need, and how urgently do we need to provide this help? And I think precision palliative care really mirrors the logic and the philosophy of precision oncology. So just like we've made strides trying to match therapies to tumor biology, we also need to have the same attention and the same precision to match support to symptoms, to context of a patient situation and their caregiver, and also to their personal goals. So I think instead of a blanket referral, we really need to tailor care, the right support at the right moment for the right person to the right care teams. And I think to be more precise, there's really four core elements to allow us to do this well. So first, we really need to implement systematic screening. Let's use what we already have. Many of our centers have patient reported outcomes. The Commission on Cancer motivates us to use distress screening tools. And the EHR is there, but we do very little to flag and to surface unmet care needs. We have seen amazing work from people like Dr. Ethan Bash, who is the pioneer on patient-reported outcomes, and Dr. Ravi Parikh, who used to be my colleague at Penn, now at Emory, who show that you could use structured data and machine learning to identify some of these patient needs in real time. The second piece is after a systematic screening, we really need to build very clear referral pathways. One very good example is what the supportive care team at MD Anderson has done, of course, led by Dr. Eduardo Brera and Dr. David Huey, where they have, for example, designed condition-specific triggers. Urgent referrals, for example, to palliative care for severe symptoms, where they talk about it like a rapid response team. They will see them within 72 hours of the flag. But at the same time, if the unmet need is a caregiver distress, perhaps the social work referral is the first part of the palliative care intervention that needs to be placed. And I think this helps create both clarity and consistency but also it pays attention to that provider and availability demand mismatch. Third, I really think we need to triage smartly. As mentioned in the prior example, not every patient needs every team member of the palliative care team. Some benefit most from the behavioral health intervention. Others might benefit from chaplaincy or the clinician for symptom management. And I think aligning intensity with complexity helps us use our teams wisely. Unfortunately, the greatest barrier in all of our health care systems is time and time availability. And I think this is one strategic approach that I have not yet seen used very wisely. And fourth, I really think we need to embrace interdisciplinary care and change our healthcare systems to focus more on value. So this isn't about more consults or RVUs. I think it's really about leveraging our team strengths. Palliative care teams or supportive care teams usually are multidisciplinary in their core. They often have psychologists, social workers, sometimes they have nurse navigators. And I think all of these are really part of that engine of whole person care. But unfortunately, we still are not set up in care delivery systems that unfortunately to this day still model fee for service where the clinician or the physician visit is the only quote unquote real value add. Hopefully as our healthcare systems focus more on delivery and on value, this might help really embrace the structure to bring through the precision palliative care approach. Dr. Joseph McCollom: No, I love those points. You know, we talk frequently in the interdisciplinary team about how a social worker can spend 5 minutes doing something that I could not as a physician spend an hour doing. But does every patient need every member every time? And how do we work as a unified body to deliver that dose of palliative care, specialized palliative care to those right patients and match them? And I think that perfect analogy is in oncology as a medical oncologist, frequently I'm running complex next-generation sequencing paneling on patients' tumors, trying to find out is there a genetic weakness? Is there a susceptibility to a targeted therapy or an immunotherapy so that I can match and do that precision oncology, right patient to the right drug? Similarly, we need to continue to analyze and find these innovative ways like you've talked about, PROs, EHR flags, machine learning tools, to find those right patients and match them to the right palliative care interdisciplinary team members for them. I know we both get to work in oncology spaces and palliative and supportive spaces in our clinical practice. Share a little bit, if you could, Ramy, about what that looks like for your practice. How do you find those right patients? And how do you then intervene with that right palliative oncology dose? Dr. Ramy Sedhom: So Joe, when I first started in this space as a junior faculty, one thing became immediately clear. I think if we rely solely on physicians to identify the patients for palliative care, we're unfortunately going to be very limited by what we individually, personally observe. And I think that's what reflects the reality that many patients have real needs that go unseen. So over the past few years, I've really worked with a lot of my colleagues to really work the health system to change that. The greatest partnership I've personally had has been working with our informatics team to build a real time EHR integrated dashboard that I think helps us give us a broader view of patient needs. What we really think of as the population health perspective. Our dashboard at Penn, for example, pulls in structured data like geriatric assessment results, PHQ-4 screens, patient reported outcomes, whether or not they've been hospitalized, whether or not these hospitalizations are frequent and recurrent. And I think it's allowed us to really move from a reactive approach to one that's more proactive. So let me give you a practical example. So we have embedded in our cancer care team, psycho-oncologists. They share the same clinic space, they're right down the hall. And we actually use this shared dashboard to review weekly trends in distress scores and patient reported outcomes. And oftentimes, if they see a spike in anxiety or worsening symptoms like depression, they'll reach out to me and say, “Hey, I noticed Mrs. Smith reported feeling very anxious today. Do you think it'd be helpful if I joined you for her visit?” And I think that's how we could really use data and teamwork to offer and maximize the right support at the right time. Like many of our other healthcare systems, we also have real-time alerts for hospitalizations. And I think like Dr. Temel's most recent trial, which we'll discuss at some point, I'm sure, it's another key trigger for vulnerability. I think whenever someone's admitted or discharged, we try to coordinate with our palliative care colleagues to assess do they need follow-up and in what timeline. And we know that these are common triggers, progression of disease, hospitalizations, drops in quality-of-life. And it's actually surprisingly simple to implement once you set up the right care structures. And I think these systems don't just help patients, which is what I quickly learned. They also help us as clinicians too. Before we expanded our team, I often felt this weight, especially as someone dual trained in oncology and palliative medicine, as trying to be everything to everyone. I remember one patient in particular, a young woman with metastatic breast cancer who was scheduled for a routine pre-chemo visit with me. Unfortunately, on that day, she had a very dramatic change in function. We whisked her down to x-ray and it revealed a pretty large pathologic fracture in her femur. And suddenly what was scheduled as a 30-minute visit became a very complex conversation around prognosis, urgent need for surgery and many, many life changes. And when I looked at my Epic list, I had a full waiting room. And thankfully, because we have embedded palliative care in our team, I was able to bring in Dr. Collins, the physician who I work with closely, immediately. She spent the full hour with the patient while I was able to continue seeing other patients that morning. And I think that's what team-based care makes possible. It's not just more hands on deck but really optimizing the support the patient needs on each individual day. And I think last, we're also learning a lot from behavioral science. So many institutions like Penn, Stanford, Massachusetts General, they've experimented with a lot of really interesting prompts in the EHR. One of them, for example, is the concept of nodes or the concept of prompt questions. Like, do you think this patient would benefit from a supportive care referral? And I think these low-level nudges, in a sense, can actually really dramatically increase the uptake of palliative care because it makes what's relevant immediately salient and visible to the practicing physician. So I think the key, if I had to maybe finish off with a simple message: It's not flashy tech, it's not massive change against staffing, but it's having a local champion and it's working smarter. It's asking the questions of how can we do this better and setting up the systems to make them more sustainable. Dr. Joseph McCollom: I appreciate you talking about this because I think a lot of folks want to put the wheels on in some way and they don't know where to get started. And so I think some of the models that you've been able to create, being able to track patients, screen your population, find the right individuals, and then work within that team to be able to extend, I think when you have an embedded palliative care specialist in your clinic, they expand your practice as a medical oncologist. And so you can make that warm handoff. And that patient and that caregiver, when they view the experience, they don't view you as a medical oncologist, someone else as a palliative care specialist, they view that team approach. And they said, "The team, my cancer team took care of me." And I think we can really harness a lot of the innovative technological advancements in our EHR to be able to prompt us in this work. I know that Dr. Temel had kind of set the stage for early palliative care intervention, and you did mention her stepped palliative care trial. Where do you see some of the future opportunities as we continue to push the needle forward as oncologists and palliative care specialists? What do you see as being the next step? Dr. Ramy Sedhom: So for those who are not familiar with the stepped palliative care trial, again, work by Dr. Temel, I think it's really important to explain not just the study itself, but I think more importantly, what it's representing for the future of our field. First, I really want to acknowledge Dr. Temel, who is a trailblazer in palliative oncology. Her work has not only shaped how we think about timing and delivery, but really about the value of supportive care. And more importantly, I think for all the young trainees listening, she had shown that rigorous randomized trials in palliative care are possible and meaningful. And I think for me, one quick learning point is that you could be an oncologist and lead this impactful research. And she's inspired many and many of us. Now let's quickly transition to her study. So in this trial, the stepped palliative care trial, patients with advanced lung cancer were randomized into two groups. One group followed the model from her landmark 2010 New England Journal of Medicine paper, which was structured monthly palliative care visits, again, within eight weeks of diagnosis. The second group, which is in this study, the intervention or the stepped palliative care group, received a single early palliative care visit. Think of this as a meet and greet. And then care was actually stepped up. If one of three clinical triggers happened. One, a decline in patient reported quality of life as measured by PROs. Two, disease progression, or three, hospitalization. And the findings which were presented at ASCO 2024 were striking. Clinical outcomes, very similar between the two groups. And this included quality-of-life, end-of-life communication, and resource use. But I think the take-home point is that the number of palliative care visits in the stepped group was significantly lower. So in other words, same impact and fewer visits. This was a very elegant example of how we can model precision palliative care, right sizing patient care based on patient need. So where do we go from here? I think if we want this model to take root nationally, we really need to pull on three key levers: healthcare systems, healthcare payment, and healthcare culture. So from a system alignment, unfortunately, as mentioned too often, the solution to gaps in palliative care is we need more clinicians. And while yes, that's partly true, it's actually not the full picture. I think what we first need to do and what's more likely to be achieved is to develop systems that focus on building the infrastructure that maximizes the reach of our existing care teams. So this means investing in nurse navigation, real-time dashboards with patient-reported outcomes and EHR flags, and again, matching triage protocols where intensity matches complexity. And the goal, as mentioned, isn't to maximize consults, but to really maximize deployment of expertise based on need. The second piece is, of course, we need payment reform. So the stepped palliative care model only works when it allows continuous patient engagement. But unfortunately, current pay models don't reward or incentivize that. In fact, electronic PROs require a very high upfront financial investment and ongoing clinician time with little to no reimbursement. Imagine if we offered bundled payments or value-based incentives for teams that integrated PROs. Or imagine if we reimbursed palliative care based on impact or infrastructure instead of just fee-for-service volume. There is a lot of clear evidence that tele-palliative care is effective. In fact, it was the Plenary at ASCO 2024. Yet we're still battling these conversations around inconsistent reimbursement, and we're always waiting on whether or not telehealth waivers are gonna continue. So I think most importantly is we really need to recognize the broader scope of what palliative care offers, which is caregiver support, improving navigation, coordinating very complex transitions. To me, and what I've always prioritized as a champion at Penn, is that palliative care is not a nice to have, and neither are all of these infrastructures, but they're really essential to whole person care, and they need to be financially supported. And last, we really need a culture shift. We need to change from how palliative care is perceived, and it can't be something other. It can't be something outside of oncology, but it really needs to be embraced as this is part of cancer care itself. I often see hesitancy from many oncologists about introducing palliative care early. But it doesn't need to be a dramatic shift. I think small changes in language, how we introduce the palliative care team, and co-management models can really go a very long way in normalizing this part of patient care. And I'm particularly encouraged, Joe, by one particular innovation in this space, which is really the growth of many startups. And one startup, for example, is Thyme Care, where I've seen them working with many, many private practices across the country, alongside partnerships with payers to really build tech-enabled navigation that tries to basically maximize triage support with electronic PROs. And to me, I really think these models can help scale access without overwhelming current care teams. So precision palliative care, Joe, in summary, I think should be flexible, scalable, and really needs to align based on what patients need. Dr. Joseph McCollom: No, I really appreciate, Ramy, you talking about that it really takes a village to get oncology care in both a competent and a compassionate way. And we need buy-in champions at all levels: the system level, the administrative level, the policy level, the tech level. And we need to change culture. I kind of want to just get your final impressions and also make sure that we make our listeners aware of our article. We should be able to have this in the show notes here as well to find additional tools and resources, all the studies that were discussed in today's episode. But, Ramy, what are some of your kind of final takeaways and conclusions? Dr. Ramy Sedhom: Before we wrap up, I just want to make sure we highlight a very exciting opportunity for residents considering a future in oncology and palliative medicine. Thanks to the leadership of Dr. Jamie Von Roen, who truly championed this cause, ASCO and the ABIM (American Board of Internal Medicine) have partnered to create the first truly integrated palliative care oncology fellowship. Trainees can now double board in just two years or triple board in three with palliative care, oncology, and hematology. And I think, Joe, as you and I both know, it's incredibly rewarding and meaningful to work at this intersection. To close our message, if there's one message I think listeners should carry with them, it's that palliative care is about helping people live as well as possible for as long as possible. And precision palliative care simply helps us do that better. We need to really develop systems that tailor support to individual need, value, and individual goals. Just like our colleagues in precision oncology mentioned, getting the right care to the right patient at the right time, and I would add in the right way. For those who want to learn more, I encourage you to read our full article in JCO, which is “Precision Palliative Care As a Pragmatic Solution for a Care Delivery Problem.” Joe, thank you so, so much for this thoughtful conversation and for your leadership in our field. And thank you to everyone for listening. Thank you all for being champions of this essential part of cancer care. If you haven't yet joined the ASCO Palliative Care Communities of Practice, membership is free, and we'd love to have you. Dr. Joseph McCollom: Thank you, Ramy, not only for sharing your insights today, but the pioneering work that you have done in our field. You are truly an inspiration to me in clinical practice, and it is an honor to call you both a colleague and friend. And thank you for our listeners for joining us today. If you value the insights that you've heard on the ASCO Daily News Podcast, please subscribe, rate, and review wherever you get your podcasts. Thanks again. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:  Dr. Joseph McCollom @realbowtiedoc Dr. Ramy Sedhom @ramsedhom Follow ASCO on social media:  @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook  ASCO on LinkedIn  Disclaimer: Dr. Joseph McCollom: No relationships to disclose Dr. Ramy Sedhom: No relationships to disclose

Ep. 561 Dosimetry University VI: Challenging Case Review with Dr. Tyler Sandow and Dr. Zach Berman

women management fda hormones evaluating menopause uc san diego hormone therapy history behind gsm lastra jco health initiative whi

Play Episode Listen Later Jul 29, 2025 48:55

When is Y90 the right treatment for metastatic disease? Join Drs. Tyler Sandow, Zach Berman and host Kavi Krishnasamy in the conclusion of Dosimetry University where they discuss the complexities of treating different variations of metastatic disease and review how they've approached complicated cases with Y90. --- SYNPOSIS The interventional oncologists first outline the types of metastases that they treat, including colorectal, lung, cholangiocarcinoma, breast, gastric, RCC, and melanoma. The doctors then discuss the potential for Y90 to provide palliative relief by reducing tumor-related pain. The conversation also covers key differences between treating liver-dominant and liver-only disease, along with their algorithm for patients not on systemic chemotherapy.The episode then covers advanced concepts in Y90, such as sub-ablative dosing, the possibility of creating an abscopal effect, and how radiation thresholds change depending on treatment goals. They outline their approach to partition dosimetry, using SPECT/CT to calculate tumor-to-normal ratios, and explain how they modify particle counts and microsphere activity, using flow augmentation based on tumor vascularity. Additional discussion includes the impact of mutation status, prior lines of chemotherapy, and tumor response criteria like RECIST 1.1 and mRECIST. The experts conclude with a case series that illustrates decision-making around when to consider Y90, thermal ablation, TACE, or alternative approaches—even in complex cases like sphincter of Oddi dysfunction. The session underscores the nuanced nature of advanced dosimetric techniques and the evolving landscape of interventional oncology. --- TIMESTAMPS 00:00 - Introduction 01:30 - Types of Metastases Treated with Y9002:50 - Liver-Dominant vs. Liver-Only Disease 07:20 - Sub-Ablative Dosing and the Abscopal Effect09:55 - Tips for Partition Dosimetry 15:30 - Clinical Factors in Treatment Planning23:50 - Choosing Ablation, Resection, or Y90 for mCRC30:27 - Case Series: Colorectal Metastases, Biliary Complications, and more46:00 - Final Thoughts: The Evolving Field --- RESOURCES RECIST 1.1 and mRECIST Criteria:https://pmc.ncbi.nlm.nih.gov/articles/PMC9161105/ COLLISION Trial:https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA3501 BackTable Episode on COLLISION Trial:https://www.youtube.com/watch?v=NQLKcv1BRVM FOXFIRE, SIRFLOX, FOXFIRE-Global:https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30457-6/fulltext

university tips types challenging rcc sandow resection tace zach berman jco oddi piis1470 recist dosimetry y90

Ep. 251 Evaluating Hormone Therapy in Menopause Management with Dr. Yahir Santiago-Lastra

BackTable Urology

Play Episode Listen Later Jul 29, 2025 49:39

Is one outdated warning label standing between millions of women and safe, effective care? In this episode of BackTable Urology, Dr. Yahir Santiago-Lastra, a urologist specializing in female pelvic medicine and reconstructive surgery at UC San Diego, joins host Dr. Suzette Sutherland to discuss the black box warning on vaginal estrogen, its historical context, and the ongoing advocacy efforts to update outdated FDA guidelines. --- SYNPOSIS The conversation covers the importance of low-dose vaginal estrogen in treating genitourinary syndrome of menopause (GSM), the fear surrounding hormone therapy due to misinterpreted data from the Women's Health Initiative (WHI) study, and the inequities faced in women's health, particularly in the context of hormone replacement therapies. They discuss the legislative and advocacy strategies needed to enact change, emphasizing the role of professional societies, legislative efforts, patient advocacy, and industry support in overcoming the barriers to updating the black box warning. --- TIMESTAMPS 00:00 - Introduction03:43 - History Behind the Estradiol Black Box Warning13:44 - The FDA Citizen Petition18:18 - Gender Inequity in Medicine24:05 - The Role of Organizational Guidelines in Patient Advocacy28:51 - Vaginal Estrogen for Genitourinary Syndrome of Menopause (GSM)32:57 - Medicare Spending and Legislative Advocacy44:56 - Recap and Future Directions --- RESOURCES (TRAVERSE Trial) Cardiovascular Safety of Testosterone-Replacement Therapyhttps://www.nejm.org/doi/full/10.1056/NEJMoa2215025 Systemic or Vaginal Hormone Therapy After Early Breast Cancer: A Danish Observational Cohort Studyhttps://doi.org/10.1093/jnci/djac112 (ASCO Study) Use of local estrogen therapy among breast cancer patients in SEER-MHOS databasehttps://doi.org/10.1200/JCO.2025.43.16_suppl.578 Vaginal estrogen use in breast cancer survivors: a systematic review and meta-analysis of recurrence and mortality riskshttps://doi.org/10.1016/j.ajog.2024.10.054

JCO Article Insights: IMS-IMWG Consensus on High-Risk Multiple Myeloma

Play Episode Listen Later Jul 28, 2025 24:50

In this JCO Article Insights episode, Michael Hughes summarizes “International Myeloma Society and International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma" by Avet-Loiseau et al. published on June 09, 2025 along with an interview with author Dr Nikhil C. Munshi, MD. TRANSCRIPT Michael Hughes: Welcome to this episode of JCO Article Insights. This is Michael Hughes, JCO's editorial fellow. Today I am interviewing Dr. Nikhil Munshi on the “International Myeloma Society and International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma” by Avet-Loiseau et al. At the time of this recording, our guest has disclosures that will be linked in the transcript. While some patients with multiple myeloma live for decades after treatment, others exhibit refractory or rapidly relapsing disease irrespective of treatment administered. We term this “high-risk myeloma.” Multiple risk stratification systems have been created, starting with the Durie-Salmon system in 1975 and evolving with the advent of novel therapeutics and novel treatment approaches. In 2015, the Revised International Staging System (R-ISS) was introduced, which incorporated novel clinical and cytogenetic markers and remained, until recently, a mainstay of risk stratification in newly diagnosed disease. Myeloma as a field has, just in the past few years, though, undergone explosive changes. In particular, we have seen groundbreaking advances not only in treatments - the introduction of anti-CD38 agents and the advent of cellular and bispecific therapies - but also in diagnostic technology and our understanding of the genetic lesions in myeloma. This has led to the proliferation of numerous trials employing different definitions of high-risk myeloma, a burgeoning problem for patients and providers alike, and has prompted attempts to consolidate definitions and terminology. Regarding cytogenetic lesions, at least, Kaiser et al's federated meta-analysis of 24 therapeutic trials, published here in the JCO in February of 2025 and recently podcasted in an interview with associate editor Dr. Suzanne Lentzsch, posited a new cytogenetic classification system to realize a shared platform upon which we might contextualize those trial results. This article we have here by Dr. Avet-Loiseau, Dr. Munshi, and colleagues, published online in early June of this year and hot off the presses, is the definitive joint statement from the International Myeloma Society (IMS) and the International Myeloma Working Group (IMWG). What is high-risk multiple myeloma for the modern era? The IMS and IMWG Genomics Workshop was held in July 2023 and was attended by international myeloma experts, collaborating to reach consensus based on large volumes of data presented and shared. The datasets included cohorts from the Intergroupe Francophone du Myélome (IFM); the HARMONY project, comprised of multiple European academic trials; the FORTE study, findings from which solidified KRd as a viable induction regimen; the Grupo Español de Mieloma Múltiple (GEM) and the PETHEMA Foundation; the German-Speaking Myeloma Multicenter Group (GMMG); the UK-based Myeloma XI, findings from which confirmed the concept of lenalidomide maintenance; Emory 1000, a large, real-world dataset from Emory University in Atlanta; the Multiple Myeloma Research Foundation Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass) dataset; and some newly diagnosed myeloma cohorts from the Mayo Clinic. Data were not pooled for analyses and were assessed individually - that is to say, with clear a priori understanding of whence the data had been gathered and for what original purposes. Consensus on topics was developed based on the preponderance of data across studies and cohorts. In terms of results, substantial revisions were made to the genomic staging of high-risk multiple myeloma, and these can be sorted into three major categories: A) alterations to the tumor suppressor gene TP53; B) translocations involving chromosome 14: t(14;16) (c-MAF overexpression), t(14;20) (MAFB overexpression), and t(4;14) (NSD2 overexpression); and C) chromosome 1 abnormalities: deletions of 1p or additional copies of 1q. In terms of category A, TP53 alterations: Deletion of 17p is present in up to 10% of patients at diagnosis and is enriched in relapsed or refractory disease. This is well-documented as a high-risk feature, but the proportion of the myeloma cells with deletion 17p actually impacts prognosis. GEM and HARMONY data analyses confirmed the use of 20% clonal cell fraction as the optimal threshold value for high-risk disease. That is to say, there must be the deletion of 17p in at least 20% of the myeloma cells on a FISH-analysis of a CD138-enriched bone marrow sample to qualify as high-risk disease. TP53 mutations can also occur. Inactivating mutations appear to have deleterious effects similar to chromosomal losses, and the biallelic loss of TP53, however it occurs, portends particularly poor prognosis. This effect is seen across Myeloma XI, CoMMpass, and IFM cohorts. Biallelic loss is rare, it appears to occur in only about 5% of patients, but next-generation sequencing is nevertheless recommended in all myeloma patients. Category B, chromosome 14 translocations: Translocation t(14;16) occurs in about 2% to 3% of patients with newly diagnosed disease. In the available data, primarily real-world IFM data, t(14;16) almost always occurs with chromosome 1 abnormalities. Translocation t(4;14) occurs in about 10% to 12% of newly diagnosed disease, but only patients with specific NSD2 alterations are, in fact, at risk of worse prognosis, which clinically appears to be about one in every three of those patients. And so together, the CoMMpass and Myeloma XI data suggest that translocation t(4;14) only in combination with deletion 1p or gain or amplification of 1q correlates with worse prognosis. Translocation t(14;20) occurs in only 2% of newly diagnosed disease. Similar to translocation t(4;14), it doesn't appear to have an effect on prognosis, except if the translocation co-occurs with chromosome 1 lesions, in which case patients do fare worse. Overall, these three translocations - t(14;16), t(4;14), and t(14;20) - should be considered high-risk only if chromosome 1 aberrations are also present. In terms of those chromosome 1 aberrations, category C, first deletions of 1p: Occurring in about 13% to 15% of newly diagnosed disease, deletion 1p eliminates critical cell checkpoints and normal apoptotic signaling. In the IFM and CoMMpass dataset analyses, biallelic deletion of 1p and monoallelic deletion of 1p co-occurring with additional copies of 1q denote high-risk. In terms of the other aberration in chromosome 1 possible in myeloma, gain or amplification of 1q: This occurs in up to 35% to 37% of newly diagnosed disease. It upregulates CKS1B, which is a cyclin-dependent kinase, and ANP32E, a histone acetyltransferase inhibitor. GEM and IFM data suggest that gain or amplification of 1q - there was no clear survival detriment to amplification - is best considered as a high-risk feature only in combination with the other risk factors as above. Now, in terms of any other criteria for high-risk disease, there remains one other item, and that has to do with tumor burden. There has been a consensus shift, really, in both the IMS and IMWG to attempt to develop a definition of high-risk disease which is based on biologic features rather than empirically observed and potentially temporally dynamic features, such as lactate dehydrogenase. Beta-2 microglobulin remains an independent high-risk indicator, but care must be taken when measuring it, as renal dysfunction can artificially inflate peripheral titers. The consensus conclusion was that a beta-2 microglobulin of at least 5.5 without renal failure should be considered high-risk but should not preclude detailed genomic profiling. So, in conclusion, the novel 2025 IMS-IMWG risk stratification system for myeloma is binary. It's either high-risk disease or standard-risk disease. It's got four criteria. Number one, deletion 17p and/or a TP53 mutation. Clonal cell fraction cut-off, remember, is 20%. Or number two, an IGH translocation - t(4;14), t(14;16), t(14;20) - with 1q gain and/or deletion of 1p. Or a monoallelic deletion of 1p with 1q additional copies or a biallelic deletion of 1p. Or a beta-2 microglobulin of at least 5.5 only when the creatinine is normal. This is a field-defining work that draws on analyses from across the world to put forward a dominant definition of high-risk disease and introduces a new era of biologically informed risk assessment in myeloma. Now, how does this change our clinical approach? FISH must be performed on CD138-enriched samples and should be performed for all patients. Next-generation sequencing should also be performed on all patients. Trials will hopefully now begin to include this novel definition of high-risk multiple myeloma. It does remain to be seen how data from novel therapeutic trials, if stratified according to this novel definition, will be interpreted. Will we find that therapies being evaluated at present have differential effects on myelomas with different genetic lesions? Other unanswered questions also exist. How do we go about integrating this into academic and then community clinical practice? How do we devise public health interventions for low-resource settings? To discuss this piece further, we welcome the esteemed Dr. Nikhil Munshi to the podcast. Dr. Munshi is a world-renowned leader in multiple myeloma and the corresponding author on this paper. As Professor of Medicine at Harvard Medical School, Director of the Multiple Myeloma Effector Cell Therapy Unit, and Director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center of the Dana-Farber Cancer Institute, he has presided over critical discoveries in the field. Thank you for joining us, Dr. Munshi. Dr. Nikhil Munshi: Oh, it's my pleasure being here, Michael, to discuss this interesting and important publication. Michael Hughes: I had a few questions for you. So number one, this is a comprehensive, shall we say, monumental and wide-ranging definition for high-risk myeloma. How do you hope this will influence or impact the ways we discuss myeloma with patients in the exam room? And how do we make some of these components recommended, in particular next-generation sequencing, feasible in lower-resource settings? Dr. Nikhil Munshi: So those are two very important questions. Let's start with the first: How do we utilize this in our day-to-day patient care setting? So, as you know well, we have always tried to identify those patients who do not do so well with the current existing treatment. And for the last 30 years, what constitutes a myeloma of higher risk has continued to change with improvement in our treatment. The current definition basically centers around a quarter of the patients whose PFS is less than 2 to 3 years. And those would require some more involved therapeutic management. So that was a starting point of defining patients and the features. As we developed this consensus amongst ourselves - and it's titled as “International Myeloma Society, International Myeloma Working Group Consensus Recommendation” - this IMS-IMWG type of recommendation we have done for many years, improvising in various areas of myeloma care. Now, here, we looked at the data that was existing all across the globe, utilizing newer treatment and trying to identify that with these four-drug regimens, with transplant and some of the immunotherapy, which group of patients do not do as well. And this is where this current algorithm comes up. So before I answer your question straight, “How do we use it?” I might like to just suggest, “What are those features that we have identified?” There are four features which constitute high-risk disease in the newer definition. Those with deletion 17p with 20% clonality and/or TP53 mutation. Number two, patients with one of the translocations - t(4;14), t(14;16), or t(14;20) - co-occurring with 1q amplification or deletion 1p32. And that's a change. Previously, just the translocation was considered high-risk. Now we need a co-occurrence for it to be called high-risk. The third group is patients having biallelic deletion 1p32 or monoallelic deletion 1p32 along with 1q amplification. And finally, patients with high beta-2 microglobulin, more than or equal to 5.5 mg/dL, with normal creatinine less than 1.2 mg/dL. And the question, “How do we use this?” There are multiple areas where we incorporate high-risk features in our treatment algorithm. One of the first areas is where we would consider the induction regimen. If a patient has a high-risk disease, we would definitely consider a four-drug regimen rather than a three-drug regimen, although we are beginning to incorporate four-drug for all groups. That's one important thing. Number two, those are the patients where we do consider consolidation with transplant or maybe in the new world, considering some of the immunotherapeutic consolidation more early or more aggressively. Number three, these are the patients who get a little bit more maintenance therapy. So normally, lenalidomide might end up being our standard maintenance regimen. In patients who have high-risk disease, we incorporate either addition of daratumumab or the anti-CD38 targeting antibody and/or addition of proteasome inhibitor, either bortezomib or carfilzomib. So you would have multi-drug maintenance therapy in these patients. And in high-risk patients, we follow them with maintenance longer periods of time. One very critically important point to keep in mind is that to get the better outcome in high-risk disease, we must try to get them into MRD negativity because there is clear data that patients who do achieve MRD negativity, despite having high-risk disease, have a much superior outcome. They become near to standard-risk disease. And so, in high-risk patients, I would try to do whatever various options I have to try and get them into MRD-negative status. And when these patients relapse, we do not wait for the classic progression criteria to be met before we intervene. We would propose and suggest that we intervene earlier before the disease really blasts off. And so there are a number of areas in our setting where this high-risk definition will help us intervene appropriately and also with appropriate aggressiveness to achieve better outcome, to make this similar to standard-risk disease. Michael Hughes: Thank you, Dr. Munshi. And thoughts on how to really integrate this not only into academic centers but also lower-resource settings? Dr. Nikhil Munshi: So that's a very important question, Michael. And when we were developing this consensus, we were very cognizant of that fact. So wherever available, I think we are recommending that over a period of next 2, 3, 5 years, we should begin to switch over to sequencing-based methods because two components of this definition, one is TP53 mutation, which we cannot do without sequencing, and also reliably detecting deletion 1p requires sequencing-based method. So in the low-resource countries - and there are many in this world, and also even in our own country, patients may not be able to afford it - the older method with FISH or similar such technology, which is more affordable, is also acceptable for current time. They may miss a very small number of patients, maybe 2% to 3%, where these finer changes are not picked up, but a majority of this would be captured by them. So the current practice might still be applicable with some limitation in those patient populations, and that's what we would recommend. What is happening, fortunately, is that actually sequencing-based method is becoming cheaper. And in many centers, it is cheaper to do the sequencing rather than to do the FISH analysis. And so my hope is that even in low-resource centers, sequencing might be more economical in the end. It's, I think, the access to technology, which is a little bit limited currently, but it's hopefully becoming available soon. Michael Hughes: Thank you, Dr. Munshi. And staying for a minute and looking at the multiple myeloma subsets which might be missed by this really still very broad-ranging high-risk definition, at least by prior risk stratification systems, right, there is this group of patients who have standard-risk cytogenetics by R-ISS or R2-ISS, but they have primary refractory disease or they relapse early. We call these, as you are well aware, functionally high-risk disease. What proportion of previously FHR, functionally high-risk, myeloma patients do you expect to be captured by this novel definition? Dr. Nikhil Munshi: So I think the newer definition - and we can look at it both ways, but the newer definition should capture most of the functionally high-risk definition. To put it differently, Michael, there are patients who we know are, as you mentioned, functionally high-risk. Those are the patients who might have plasma cell leukemia, those who might have extramedullary disease, those who might not respond to our four-drug induction. If you don't respond to the four-drug induction, almost by definition, they are high-risk. However, a majority of them have one of the abnormalities that we are describing here. There would be a very small proportion which may not have. And if they do not have, we know one of the important components of this definition here is also that the genome, we know, keeps on evolving. So there may be a very small clone with the high-risk feature which was not obvious in the beginning. Following treatments or following relapse, that clone predominates, and now the patient's disease becomes high-risk. So the definition would incorporate or would capture these functional high-risk patients, but as you said, in countries where resources are not available, using this functional high-risk would also be helpful and advantageous. Sometimes LDH ends up being a high-risk. In our studies, LDH has not come out to be high-risk anymore because the features we are describing captures most of those patients, but those alternatives, older, can still be considered if other newer techniques are not available. Michael Hughes: Got you. And in terms of these older definitions, yes, that incorporate tumor burden, these empirical observations about how myeloma presents, do you foresee any additional tumor burden indicators being added to future definitions of high-risk disease? Or do you instead see this particular definition as a major waypoint on the journey towards a fully biologically grounded definition of high-risk disease? Dr. Nikhil Munshi: I think your second part is what is going to happen. I think the tumor burden-related definition is being now replaced by the biological or genomic-based definition. And I think at some point, it will be quite fully replaced. One component not here, and it is because one thing, we don't have enough data; number two, we don't know how it will pan out, is also the influence of the microenvironment on the risk definition. For example, the immune system, the immune function, etc. But not enough data exists to suggest how it would change the current definition. So in future, would a definition be totally genomic or it could be more integrative? And my personal guess is that it would be more integrative and that some immune features might come into the picture, especially now that we are using immune-based therapy as a very important component of treatment - CAR T-cells, bispecific, and antibody-based treatments. What role the immune system plays in either supporting tumor or what role suppression of the anti-tumor immunity plays? They all will be important how patient outcomes end up being, and which in turn could translate into how patient's risk stratification might happen. So I think the older tumor burden-related definitions probably will become things of the past. What we have currently proposed and consensus developed is the new path forward, and over time, some microenvironmental influences, if defined and found to be important, may get some more incorporation if it compares favorably with the genomic features. Michael Hughes: Thank you, Dr. Munshi for that enlightening response. To conclude the podcast, I'd like to look to the future and to the immediate future, what are the next steps for high-risk disease definition between now and discussing an integrated genomic-microenvironment-based definition? Will we see attempts to refine? Will we see a multi-level system, things like this? Dr. Nikhil Munshi: Yeah, so I think the current definition will be here to stay for the next 10 years or so. I think this has been developed using a large amount of data, so we do believe that this will remain fine. It has been validated now within the last six months by a few of the other studies. So there won't be a quick change. But we will try to, all of us will try to innovate. And as you very rightly bring up, the areas of research would include looking at the expression or transcriptomic component. Does that matter? And we do believe a small number of patients will have transcriptomic changes, not looked at the DNA changes, and may play a role. There are newer components, so long non-coding RNA, for example, is going to be an important component to look at, how it impacts the disease outcome, etc. There are also some of the proteomic-related changes which may become important in our studies. And then as we discussed, microenvironment and immunological changes. So these are the future areas of ongoing research where we all should collect data, and then in the next 5 to 10 years, we'll have another group meeting to see has anything changed or any of the features have become more important. Most of the time, some of the older features are lost because they are not as critically high-risk, and the newer features come in. And so the historical background for just one second, there was a time when chromosome 13 was considered a high-risk disease. We now don't even mention it because it's not high-risk. The newer treatments have improved the outcome. t(4;14) used to be a high-risk disease. Now by itself today, in this definition by itself is not; it needs to be with something else. And so I think this is a great sign of progress. As we improve the treatment and outcomes, some of the features will become less important, new features will come up, and we'll need to keep on evolving with time and with technology and make it better for patients. Michael Hughes: Thank you so much, Dr. Munshi, for your wisdom, for your sagacity, for your historical perspective as well. Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries. And be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Episode 63. Management of Follicular Lymphoma with Dr. Gilles Salles

management cancer patients phase prima relevance supplement gilles salles hematology memorial sloan kettering cancer center rct relapsed trog lba follicular lymphoma jco rituximab systemic therapy

Play Episode Listen Later Jul 25, 2025 51:37

In this episode, we discuss the management of follicular lymphoma with Dr. Gilles Salles from Memorial Sloan Kettering Cancer Center. Here are the articles we discussed: 1. Relevance of Bone Marrow Biopsy in Follicular Lymphoma: https://pubmed.ncbi.nlm.nih.gov/35787017/2. TROG 99.03 (RCT of Systemic Therapy after Involved-Field Radiotherapy in Patients with Early-Stage Follicular Lymphoma): https://pubmed.ncbi.nlm.nih.gov/29975623/3. Long-term follow-up results of RCT comparing early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumor burden follicular lymphoma: https://pubmed.ncbi.nlm.nih.gov/40306831/4. RELEVANCE RCT: Lenalidomide plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma: https://ascopubs.org/doi/10.1200/JCO.22.008435. GALLIUM RCT: Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL. https://pubmed.ncbi.nlm.nih.gov/37404773/https://pubmed.ncbi.nlm.nih.gov/28976863/6. Long-term follow-up of mosunetuzumab in relapsed/refractory FL: https://pubmed.ncbi.nlm.nih.gov/39447094/7. Epcoritamab in relapsed/refractory FL: https://pubmed.ncbi.nlm.nih.gov/38889737/8. Phase 3 inMIND RCT: Tafasitamab plus Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma: https://ashpublications.org/blood/article/144/Supplement%202/LBA-1/5343199. Long term follow-up results from the Phase 3 PRIMA trial of rituximab maintenance in Follicular Lymphoma: https://ascopubs.org/doi/10.1200/JCO.19.01073

Clinical Challenges in Colorectal Surgery: Early Onset Colorectal Cancer

Behind The Knife: The Surgery Podcast

Play Episode Listen Later Jul 21, 2025 38:35

The incidence of early onset colorectal cancer (EOCRC) has been rising prompting the change in change in screening guidelines to 45 years of age for average risk patients. Join us for an in-depth discussion with guest speakers Dr. Andrea Cercek and Dr. Nancy You, where we provide a comprehensive look at the growing challenge of EOCRC. Hosts: - Dr. Janet Alvarez - General Surgery Resident at New York Medical College/Metropolitan Hospital Center - Dr. Wini Zambare – General Surgery Resident at Weill Cornell Medical Center/New York Presbyterian - Dr. Phil Bauer, Graduating Colorectal Surgical Oncology Fellow at Memorial Sloan Kettering Cancer Center - Dr. J. Joshua Smith MD, PhD, Chair, Department of Colon and Rectal Surgery at MD Anderson Cancer Center - Dr. Andrea Cercek - Gastrointestinal Medical Oncologist at Memorial Sloan Kettering Cancer Center - Dr. Y. Nancy You, MD MHSc - Professor, Department of Colon and Rectal Surgery at MD Anderson Cancer Center Learning objectives: - Describe trends in incidence of colorectal cancer, with emphasis on the rise of EOCRC. - Identify age groups and demographics most affected by EOCRC. - Summarize USPSTF recommendations for colorectal cancer screening. - Distinguish between screening methods (e.g., colonoscopy, FIT-DNA) and their sensitivity. - Understand treatment approaches for colon and rectal cancer (CRC) - Understand the role of mismatch repair (MMR) status in guiding treatment. - Outline the importance of genetic counseling and testing in young patients. - Discuss racial, ethnic, and socioeconomic disparities in CRC incidence and outcomes. - Describe the impact of cancer treatment on fertility and sexual health. - Review fertility preservation options. - Identify the value of integrated care teams for young CRC patients. References: 1. Siegel, R. L. et al. Colorectal Cancer Incidence Patterns in the United States, 1974–2013. JNCI J. Natl. Cancer Inst. 109, djw322 (2017). https://pubmed.ncbi.nlm.nih.gov/28376186/ 2. Abboud, Y. et al. Rising Incidence and Mortality of Early-Onset Colorectal Cancer in Young Cohorts Associated with Delayed Diagnosis. Cancers 17, 1500 (2025). https://pubmed.ncbi.nlm.nih.gov/40361427/ 3. Phang, R. et al. Is the Incidence of Early-Onset Adenocarcinomas in Aotearoa New Zealand Increasing? Asia Pac. J. Clin. Oncol.https://pubmed.ncbi.nlm.nih.gov/40384533/ 4. Vitaloni, M. et al. Clinical challenges and patient experiences in early-onset colorectal cancer: insights from seven European countries. BMC Gastroenterol. 25, 378 (2025). https://pubmed.ncbi.nlm.nih.gov/40375142/ 5. Siegel, R. L. et al. Global patterns and trends in colorectal cancer incidence in young adults. (2019) doi:10.1136/gutjnl-2019-319511. https://pubmed.ncbi.nlm.nih.gov/31488504/ 6. Cercek, A. et al. A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers. J. Natl. Cancer Inst. 113, 1683–1692 (2021). https://pubmed.ncbi.nlm.nih.gov/34405229/ 7. Zheng, X. et al. Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer. JNCI J. Natl. Cancer Inst. 113, 543–552 (2021). https://pubmed.ncbi.nlm.nih.gov/33136160/ 8. Standl, E. & Schnell, O. Increased Risk of Cancer—An Integral Component of the Cardio–Renal–Metabolic Disease Cluster and Its Management. Cells 14, 564 (2025). https://pubmed.ncbi.nlm.nih.gov/40277890/ 9. Muller, C., Ihionkhan, E., Stoffel, E. M. & Kupfer, S. S. Disparities in Early-Onset Colorectal Cancer. Cells 10, 1018 (2021). https://pubmed.ncbi.nlm.nih.gov/33925893/ 10. US Preventive Services Task Force. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 325, 1965–1977 (2021). https://pubmed.ncbi.nlm.nih.gov/34003218/ 11. Fwelo, P. et al. Differential Colorectal Cancer Mortality Across Racial and Ethnic Groups: Impact of Socioeconomic Status, Clinicopathology, and Treatment-Related Factors. Cancer Med. 14, e70612 (2025). https://pubmed.ncbi.nlm.nih.gov/40040375/ 12. Lansdorp-Vogelaar, I. et al. Contribution of Screening and Survival Differences to Racial Disparities in Colorectal Cancer Rates. Cancer Epidemiol. Biomarkers Prev. 21, 728–736 (2012). https://pubmed.ncbi.nlm.nih.gov/22514249/ 13. Ko, T. M. et al. Low neighborhood socioeconomic status is associated with poor outcomes in young adults with colorectal cancer. Surgery 176, 626–632 (2024). https://pubmed.ncbi.nlm.nih.gov/38972769/ 14. Siegel, R. L., Wagle, N. S., Cercek, A., Smith, R. A. & Jemal, A. Colorectal cancer statistics, 2023. CA. Cancer J. Clin. 73, 233–254 (2023). https://pubmed.ncbi.nlm.nih.gov/36856579/ 15. Jain, S., Maque, J., Galoosian, A., Osuna-Garcia, A. & May, F. P. Optimal Strategies for Colorectal Cancer Screening. Curr. Treat. Options Oncol. 23, 474–493 (2022). https://pubmed.ncbi.nlm.nih.gov/35316477/ 16. Zauber, A. G. The Impact of Screening on Colorectal Cancer Mortality and Incidence: Has It Really Made a Difference? Dig. Dis. Sci. 60, 681–691 (2015). https://pubmed.ncbi.nlm.nih.gov/25740556/ 17. Edwards, B. K. et al. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 116, 544–573 (2010). https://pubmed.ncbi.nlm.nih.gov/19998273/ 18. Cercek, A. et al. Nonoperative Management of Mismatch Repair–Deficient Tumors. New England Journal of Medicine 392, 2297–2308 (2025). https://pubmed.ncbi.nlm.nih.gov/40293177/ 19. Monge, C., Waldrup, B., Carranza, F. G. & Velazquez-Villarreal, E. Molecular Heterogeneity in Early-Onset Colorectal Cancer: Pathway-Specific Insights in High-Risk Populations. Cancers 17, 1325 (2025). https://pubmed.ncbi.nlm.nih.gov/40282501/ 20. Monge, C., Waldrup, B., Carranza, F. G. & Velazquez-Villarreal, E. Ethnicity-Specific Molecular Alterations in MAPK and JAK/STAT Pathways in Early-Onset Colorectal Cancer. Cancers 17, 1093 (2025). https://pubmed.ncbi.nlm.nih.gov/40227607/ 21. Benson, A. B. et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. JNCCN 19, 329–359 (2021). https://pubmed.ncbi.nlm.nih.gov/33724754/ 22. Christenson, E. S. et al. Nivolumab and Relatlimab for the treatment of patients with unresectable or metastatic mismatch repair proficient colorectal cancer. https://pubmed.ncbi.nlm.nih.gov/40388545/ 23. Dasari, A. et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. The Lancet 402, 41–53 (2023). https://pubmed.ncbi.nlm.nih.gov/37331369/ 24. Strickler, J. H. et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 24, 496–508 (2023). https://pubmed.ncbi.nlm.nih.gov/37142372/ 25. Sauer, R. et al. Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. N. Engl. J. Med. 351, 1731–1740 (2004). https://pubmed.ncbi.nlm.nih.gov/15496622/ 26. Cercek, A. et al. Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol. 4, e180071 (2018). https://pubmed.ncbi.nlm.nih.gov/29566109/ 27. Garcia-Aguilar, J. et al. Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. J. Clin. Oncol. 40, 2546–2556 (2022). https://pubmed.ncbi.nlm.nih.gov/35483010/ 28. Schrag, D. et al. Preoperative Treatment of Locally Advanced Rectal Cancer. N. Engl. J. Med. 389, 322–334 (2023). https://pubmed.ncbi.nlm.nih.gov/37272534/ 29. Kunkler, I. H., Williams, L. J., Jack, W. J. L., Cameron, D. A. & Dixon, J. M. Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer. N. Engl. J. Med. 388, 585–594 (2023). https://pubmed.ncbi.nlm.nih.gov/36791159/ 30. Jacobsen, R. L., Macpherson, C. F., Pflugeisen, B. M. & Johnson, R. H. Care Experience, by Site of Care, for Adolescents and Young Adults With Cancer. JCO Oncol. Pract. (2021) doi:10.1200/OP.20.00840. https://pubmed.ncbi.nlm.nih.gov/33566700/ 31. Ruddy, K. J. et al. Prospective Study of Fertility Concerns and Preservation Strategies in Young Women With Breast Cancer. J. Clin. Oncol. (2014) doi:10.1200/JCO.2013.52.8877. https://pubmed.ncbi.nlm.nih.gov/24567428/ 32. Su, H. I. et al. Fertility Preservation in People With Cancer: ASCO Guideline Update. J. Clin. Oncol. 43, 1488–1515 (2025). https://pubmed.ncbi.nlm.nih.gov/40106739/ 33. Smith, K. L., Gracia, C., Sokalska, A. & Moore, H. Advances in Fertility Preservation for Young Women With Cancer. Am. Soc. Clin. Oncol. Educ. Book 27–37 (2018) doi:10.1200/EDBK_208301. https://pubmed.ncbi.nlm.nih.gov/30231357/ 34. Blumenfeld, Z. How to Preserve Fertility in Young Women Exposed to Chemotherapy? The Role of GnRH Agonist Cotreatment in Addition to Cryopreservation of Embrya, Oocytes, or Ovaries. The Oncologist 12, 1044–1054 (2007). 35. Bhagavath, B. The current and future state of surgery in reproductive endocrinology. Curr. Opin. Obstet. Gynecol. 34, 164 (2022). 36. Ribeiro, R. et al. Uterine transposition: technique and a case report. Fertil. Steril. 108, 320-324.e1 (2017). 37. Yazdani, A., Sweterlitsch, K. M., Kim, H., Flyckt, R. L. & Christianson, M. S. Surgical Innovations to Protect Fertility from Oncologic Pelvic Radiation Therapy: Ovarian Transposition and Uterine Fixation. J. Clin. Med. 13, 5577 (2024). 38. Holowatyj, A. N., Eng, C. & Lewis, M. A. Incorporating Reproductive Health in the Clinical Management of Early-Onset Colorectal Cancer. JCO Oncol. Pract. 18, 169–172 (2022). ***Behind the Knife Colorectal Surgery Oral Board Audio Review: https://app.behindtheknife.org/course-details/colorectal-surgery-oral-board-audio-review Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more. If you liked this episode, check out our recent episodes here: https://app.behindtheknife.org/listen

united states challenges care phd european global medicine risk impact cancer treat identify adoption surgery edwards med clinical ko references screenings dixon advances addition mortality contribution schnell cells outline siegel muller colon oncology adolescents jain dis ribeiro lancet jama eng ras disparities soc chemotherapy new england journal zauber sauer jacobsen colon cancer fresco distinguish mmr mountaineer colorectal cancer oncologists crc engl curr racial disparities macpherson compr incidence ovaries zheng clin colorectal carranza kupfer uterine monge christianson ruddy her2 oncol hosts dr christenson precursors increased risk blumenfeld asia pac educ early onset preoperative strickler stoffel opin fertility preservation natl abboud rectal cancer clinical management jco irradiation socioeconomic status schrag nivolumab phang cryopreservation jemal colorectal surgery yazdani us preventive services task force pract prospective study mapk steril delayed diagnosis rectal surgery oocytes lancet oncol nancy you

S1 Ep171: Advancements and Evolving Strategies in Breast Cancer Treatment at IBC East

Oncology Peer Review On-The-Go

Play Episode Listen Later Jul 21, 2025 19:04

In this episode, CancerNetwork® spoke with breast oncologists Heather McArthur, MD; Erika Hamilton, MD; Hope Rugo, MD; and Paolo Tarantino, MD, PhD, about advances in breast cancer. These developments included recent drug approvals and ongoing research for therapeutic approaches, particularly in the areas of antibody-drug conjugates (ADCs) and CDK4/6 inhibitors, based on presentations they gave at the 25th Annual International Congress on the Future of Breast Cancer (IBC) East in New York City. Initially, McArthur, Komen Distinguished Chair in Clinical Breast Cancer Research at the Harold C. Simmons Comprehensive Cancer Center, discussed immunotherapy use in high-risk triple-negative and HER2-positive disease, the evolving role of adjuvant CDK4/6 inhibition in HER2-negative breast cancer, and potentially transformative advancements in early breast cancer treatment. She highlighted the FDA approval for pembrolizumab (Keytruda) in early-stage triple-negative breast cancer, promising clinical trials in estrogen receptor (ER)–positive high-risk early-stage breast cancer, and data from an investigator-initiated trial to treat HER2-positive disease. Additionally, she highlighted an 8.5% improvement in pathological complete response with pembrolizumab added to immunotherapy in the phase 3 KEYNOTE-756 trial (NCT03725059), adding that a further event-free survival benefit may complicate the landscape for CDK4/6 inhibition based on lung and liver toxicities associated with the coadministration of these inhibitors with immunotherapy.1 McArthur expressed further excitement for ADC-based combinations for triple-negative disease, as well as in the high-risk residual disease setting. In addition, she highlighted potential advancements in de-escalation strategies and further considerations for ADCs in the HER2-positive and hormone receptor (HR)–positive spaces. Then, Hamilton, director of Breast Cancer and Gynecologic Cancer Research at the Sarah Cannon Research Institute, highlighted emerging therapies for early breast cancer, as well as her use of datopotamab deruxtecan-dlnk (dato-DXd; Datroway) and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) given their recent approvals in various breast cancer subtypes. She also touched upon challenges with respect to the implementation of new therapies for early breast cancer into clinical practice. She initially highlighted new data from the phase 3 VERITAC-2 trial (NCT05654623) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.2 Specifically, findings showed that vepdegestrant, an oral proteolysis-targeting chimera (PROTAC), exhibited an efficacy advantage over fulvestrant (Faslodex) in patients with ESR1-mutant ER-positive, HER2-negative advanced or metastatic disease. Moreover, she highlighted data from the phase 3 DESTINY-Breast09 (NCT04784715) of T-DXd in various combinations for patients with HER2-positive metastatic breast cancer.3 Hamilton further highlighted her implementation of T-DXd into clinical practice, citing her use of the agent in patients with metastatic disease, including those with HER2-low and HER2-ultralow breast cancer. She further differentiated dato-DXd from T-DXd, suggesting that they were different classes of drugs due to their different targets: TROP2 vs HER2. She concluded by highlighting an unmet need regarding sustained benefit from endocrine therapy in HR-positive disease, as well as for ADC sequencing and mechanisms of resistance. Afterward, Rugo, division chief of Breast Medical Oncology, Women's Cancer Program Director, and professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, discussed efficacy and safety considerations for CDK4/6 inhibitors in early breast cancer treatment. Specifically, she highlighted their high tolerability despite adverse effects and costs associated with their use. Rugo further touched upon a reduction of recurrence rates associated with CDK4/6 inhibition, although longer-term follow-up data were warranted to optimize the duration of therapy and elucidate survival outcomes. Finally, Tarantino, a research fellow at the Dana-Farber Institute, concluded by discussing sequencing strategies for ADCs, as well as which breast cancer settings or patient populations will experience the greatest impact with this treatment modality. Tarantino discussed his use of the “sandwich strategy,” where he switches the mechanism of action of treatment after using a TOPO1 ADC. Furthermore, Tarantino highlighted data from the DESTINY-Breast09 and phase 3 ASCENT-04 (NCT06100874) trials, which displayed the enhanced efficacy of 2 ADC combination therapies.4 He concluded by discussing future considerations for combining multiple ADCs. References 1. Cardoso F, O'Shaughnessy J, Liu Z, et al. Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2- breast cancer: a randomized phase 3 trial. Nat Med. 2025;31(2):442-448. doi:10.1038/s41591-024-03415-7 2. Hamilton E, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study. J Clin Oncol. 2025;43(suppl 17):LBA1000. doi:10.1200/JCO.2025.43.17_suppl.LBA1000 3. Tolaney S, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): interim results from DESTINY-Breast09. J Clin Oncol. 2025;43(suppl 17):LBA1008. 4. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol. 2025;43(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109

Therapy for Stage IV NSCLC Without Driver Alterations: ASCO Living Guideline Update 2025.1 Part 1

ASCO Guidelines Podcast Series

Play Episode Listen Later Jul 17, 2025 11:30

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.

Therapy for Stage IV NSCLC With Driver Alterations: ASCO Living Guideline Update 2025.1 Part 2

ASCO Guidelines Podcast Series

Play Episode Listen Later Jul 17, 2025 15:16

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.

dna therapy journal patients iv driver guidelines georgetown university rna apple app store google play store mariposa asco stage iv alterations her2 egfr clinical oncology nsclc vegf reuss jco ros1 her3 l858r igg1 asco guidelines asco guidelines podcast

JCO Article Insights: Pooled Taletrectinib Efficacy and Safety

Play Episode Listen Later Jun 30, 2025 15:02

In this JCO Article Insights episode, host Peter Li summarizes "Taletrectinib in ROS1-Mutated Non–Small Cell Lung Cancer: TRUST" by Pérol et al, published April 03, 2025, followed by an interview with first author, Dr Maurice Pérol. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Peter Li: Welcome to this episode of JCO Article Insights. I am Dr. Peter Li, JCO's editorial fellow, and today I am joined by Dr. Maurice Pérol on “Taletrectinib in ROS1-Mutated Non–Small Cell Lung Cancer: TRUST,” by Pérol et al. At the time of this recording, our guest has disclosures that will be linked in the transcript. Before we start our interview, I want to give our listeners a quick summary of the TRUST study. For those tuning in, the TRUST study is a phase II, single-arm, open-label, nonrandomized, multicenter trial looking at the efficacy and safety of a novel, next-generation ROS1 TKI, taletrectinib, in advanced ROS1-mutated non–small cell lung cancer. While a relatively rare mutation, the prevalence of ROS1 mutations ranges from 0.9% to 2.6% of patients, with a third of patients presenting with brain mets at diagnosis.Current FDA-approved therapies include crizotinib, entrectinib, and repotrectinib, which have varying degrees of efficacy, in-coming with trade-offs in CNS penetrance and safety with newer generations, particularly in the realm of neurological side effects, highlighting an unmet need in this arena. A total of 273 patients with advanced non–small cell lung cancer with confirmed ROS1 mutation were recruited for this study. 160 patients were TKI-naive, while 113 were TKI-experienced with either crizotinib or entrectinib. Patients with asymptomatic brain mets were also allowed to enroll. In the TKI-naive arm, the median age was 57, with 91% of patients having stage IV disease, 20% having no more than one cycle of chemo, and 23% having brain mets at baseline. In the TKI-experienced arm, the median age was 53, with 97% having stage IV disease, 37% having received prior chemo, and about 50% having brain mets. Furthermore, about 10% of the study population had received entrectinib, while more than 90% had received crizotinib. About 10% had a known G2032R acquired resistance mutation. Taletrectinib was dosed at 600 mg daily until disease progression or unacceptable toxicities. The primary endpoint was overall response rate, with secondary endpoints being disease control rate, duration of response, time to response, and progression-free survival. For those with brain mets, intracranial overall response rate and disease control rate were also assessed. Median follow-up time was about 21 months in both cohorts. In the TKI-naive cohort, the overall response rate was 89%, with 8 patients achieving a complete response. Disease control rate was 95%, with a median duration of response of 44.2 months. Time to treatment response was about 1.5 months. Median progression-free survival was 45.6 months, with 52.6% not having progressed at 3 years. While overall survival data were immature, 66% of patients were still alive at 3 years. In the pretreated cohort, overall response rate was 56%, with 5 patients achieving a complete response. Overall response rate was 53% for those who were crizotinib-pretreated and 80% for the entrectinib-pretreated patients. Disease control rate was 88%, and median duration of response was about 16.5 months. Time to treatment response was also 1.5 months, and median progression-free survival was 9.7 months. Median overall survival was not reached, but 77.5% of patients were still alive at 1 year. Responses were consistently seen across subgroup analyses. 17 TKI-naive and 32 TKI-pretreated patients had measurable brain mets. In the TKI-naive arm, intracranial overall response rate was 77%. Disease control rate was 88%, and duration of response was 15 months. In the TKI-pretreated arm, intracranial overall response was 66%, with one patient achieving complete response. The disease control rate was 94%, and duration of response was about a year. For the 13 patients who had a known G2032R mutation, a 62% response rate was noted. Most common treatment-related side effects were AST/ALT elevation, nausea, and vomiting, with most being grade 1 or 2. Most common neurological side effects were dizziness, dysgeusia, and headache. Again, most were grade 1. QTc prolongation is another important adverse event to note, occurring in about 18% of all patients. Discontinuation rate from treatment was only 7%. There were three treatment-related deaths in this study: one from hepatic failure, one from pneumonia in the naive arm, and one from liver dysfunction in the pretreated arm. Dr. Peter Li: Maurice, thank you so much for joining us today to talk about your paper. Would you mind just giving yourself a brief introduction to the listeners out there of who you are? Dr. Maurice Pérol: So, my name is Maurice Perol. I'm a thoracic oncologist working in the Cancer Center of Lyon in France. And I'm involved in clinical research in thoracic oncology. I've been involved for many years now. Dr. Peter Li: Okay. And for listeners out there, don't forget, he's also the primary author of the paper that we just talked about. So, Maurice, let's begin. Can you tell our listeners what is the significance of your study? Dr. Maurice Pérol: Well, the results of these two large phase II studies - TRUST-I, which has been conducted in China, and TRUST-II, which was a global, worldwide phase II study - so, the results place taletrectinib as the TKI with the most favorable efficacy-tolerability ratio of the available ROS1-targeting TKIs, especially in frontline therapy. And this is based on the response rate, which was very impressive, the CNS penetration with a great CNS activity, the duration of response with a compelling 45 months median PFS in frontline setting. The level of activity in pretreated patients after crizotinib or entrectinib was also impressive and similar to that of repotrectinib, for example, but with a more favorable neurological tolerance profile. The toxicity is mainly represented with grade 1 or 2 transaminase elevation, but without clinical symptoms, and GI toxicity, but mainly grade 1 and 2. The neurological toxicity is low, especially for dizziness, showing that taletrectinib spares TrKB in a large part. And finally, there is also a decrease in toxicity over time, especially for GI toxicity and liver toxicities, which allows a very long and a prolonged administration, which is very important in this setting. Dr. Peter Li: These are all excellent points. Can you tell the listeners if there are any limitations that we should be concerned about, about this study? Dr. Maurice Pérol: Sure. This data comes from single-arm phase II studies. So, this is not comparative data. And a phase III trial, which compares taletrectinib to crizotinib, is ongoing to evaluate the superiority of taletrectinib over the standard of care. Another limitation comes from the lack of systematic brain imaging at each tumor evaluation in patients without brain metastases at baseline, not allowing to assess the intracranial PFS in all patients, and which did not allow us to assess the CNS protective issue from taletrectinib, especially in patients without brain metastases at baseline. Dr. Peter Li: Another question that I have is, with this novel TKI now available, how would you recommend the sequencing of these drugs? Would you start with someone on an alternate TKI and then reserve taletrectinib second line or later? Or would you use it upfront? Or does it depend? Dr. Maurice Pérol: Well, it is a very important question, as we have now different available TKIs. Looking at the efficacy-toxicity balance, I would strongly favor the use of taletrectinib in frontline setting, in first line. The response rate, the CNS activity, the duration of response with a very compelling 45 months median PFS, and moreover, the good tolerance profile over time are strong arguments in favor of giving taletrectinib in frontline. Generally speaking, the use of the most active agent as frontline treatment in lung cancer depending on an oncogenic addiction is probably the best way to improve the patient's outcome. This is true for patients with EGFR mutation, for patients with ALK fusions, and this is probably also true for patients with ROS1 fusion. So, I would probably argue in favor of a frontline use of taletrectinib. Dr. Peter Li: Listeners are going to ask, well, if you use taletrectinib upfront, then what are you going to use second line once they progress? Dr. Maurice Pérol: Well, we have some new compounds which are under development today. For example, the NVL-520, which is a very interesting compound, which seems also to be active in case of resistance mutation. But I do think that we have to use the best-in-class TKI in frontline because, you know, the extension of PFS after acquired resistance you can obtain with a second-line TKI is always shorter than the benefit you can obtain by using the most active agent in frontline. And this is true for the majority of oncogenic addiction in lung cancer. Dr. Peter Li: That makes sense. I also noticed that cognitive impairment wasn't listed in the safety table. Is that not an issue that you've observed at all with taletrectinib, or is it still an issue but less so because, like you mentioned earlier, because of its higher selectivity? Dr. Maurice Pérol: Well, this is a good question because we have some ROS1-targeting TKIs like repotrectinib, entrectinib, and even lorlatinib, with some neurological adverse events and some cognitive issues. Taletrectinib is a very selective ROS1-targeting TKI, and it spares very well the TrKB, for example, explaining that we did not observe any cognitive impairment with taletrectinib in the TRUST study, showing also with the low level of other neurological adverse events, dizziness, dysgeusia, for example, the high selectivity of the compound and the preservation of TrKB. So, this is very important when you consider the long duration of treatment in those patients with ROS1 fusion. If you have to take a drug for more than 2, 3, or 4 years, of course, the neurological adverse events are very important, and they can clearly impair the quality of life. So, this is a very important point, the very low level of neurological toxicity of taletrectinib. Dr. Peter Li: And I think that goes to say why you would favor using it frontline as well compared to entrectinib or repotrectinib. Last question that we have for you is: well, what's next? You mentioned there's a phase III trial comparing it to crizotinib. I think one of the questions that a lot of us would have is: why not compare it to one of the newer agents as a comparator arm? Dr. Maurice Pérol: Well, this is a good question. Crizotinib remains the standard of care in many countries for ROS1-positive advanced non–small cell lung cancer outside of the US, especially in Europe, and in particular in patients who do not have brain metastases at diagnosis. Entrectinib has a better CNS penetration, but it did not achieve a better PFS than crizotinib in phase I/II trials, and clearly, it has a less favorable tolerance profile with weight gain, edema, and neurological adverse events. Repotrectinib has overall a level of activity which seems close to that of taletrectinib. So, it makes it difficult to consider a comparative trial that would, for example, test taletrectinib in comparison with repotrectinib because this kind of study would need a very large number of patients and a very late readout. Considering if you have a median PFS of more than 3 or 4 years, it would be very difficult to have results in before 4-5 years. So, from a pragmatic point of view, the comparison of taletrectinib to crizotinib is probably the best way to evaluate in a phase III setting the level of activity of taletrectinib, especially in the CNS, because this study will probably allow us to assess the CNS protective effect of the compound for patients without brain metastates at baseline. So, I think probably it's a pragmatic study that will allow us to confirm the high level of activity and the good tolerance profile of taletrectinib. Dr. Peter Li: Well, thank you, Maurice, so much for speaking about the JCO article, “Taletrectinib in ROS1-Mutated Non–Small Cell Lung Cancer: TRUST,” and for all your valuable input today. Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries, and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

time trust europe china france safety patients disease iv lyon responses gi generally efficacy cns median asco cancer centers pfs egfr alk discontinuation tki pooled jco tkis qtc ros1 nvl peter li crizotinib trkb ast alt

Episode 61. Menin Inhibitors in AML with Dr. Eytan Stein

Play Episode Listen Later Jun 24, 2025 56:24

In this episode, we took a deep dive intro the landscape of menin inhibitors in AML with Dr. Eytan Stein from MSKCC. Here are the key trials and studies we discussed: ELN 2022 AML Classification https://ashpublications.org/blood/article/140/12/1345/485817/Diagnosis-and-management-of-AML-in-adults-2022Predictors of outcomes in adults with AML and KMT2A rearrangements: https://www.nature.com/articles/s41408-021-00557-6DOT1L inhibitor https://ashpublications.org/blood/article/131/24/2661/37193/The-DOT1L-inhibitor-pinometostat-reduces-H3K79AUGMENT 101: https://ascopubs.org/doi/10.1200/JCO.24.00826Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study: https://ashpublications.org/blood/article/doi/10.1182/blood.2025028357/537139/Menin-inhibition-with-revumenib-for-NPM1-mutatedKOMET-001: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00386-3/abstractSAVE trial: https://ashpublications.org/blood/article/144/Supplement%201/216/530724/Phase-I-II-Study-of-the-All-Oral-Combination-ofKOMET-007: https://library.ehaweb.org/eha/2025/eha2025-congress/4159213/harry.erba.ziftomenib.combined.with.intensive.induction.chemotherapy.2872B329.in.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2882%2Aot_id%3D31560%2Amarker%3D5843%2Afeatured%3D19595MEN1 mutations: https://www.nature.com/articles/s41586-023-05755-9

cancer diagnosis stein supplement aml augment inhibitors hematology eln eytan menin jco mskcc piis1470 npm1

Transcription: Phone Call, 2018: A Mother's Love in Illness

Oncology Peer Review On-The-Go

Play Episode Listen Later Jun 24, 2025 19:10

Listen to Journal of Clinical Oncology's Art of Oncology poem, "Transcription: Phone Call, 2018” by Elane Kim, a student at Harvard College. The poem is followed by an interview with Kim and host Dr. Mikkael Sekeres. Kim shares her poem that lingers in the spaces between words; a mother and daughter navigating illness and memory. TRANSCRIPT Narrator: Transcription: Phone Call, 2018, by Elane Kim Spiculated mass, irregular contours. Can you come to translate these words? Something in the lung. Yes, I am eating well. Birds, green ones, are nesting outside the window. Singing as if they aren't young but dying. Lately, I have been singing. Since we last spoke, the snow has melted into pearls. Rare and pale, glittering like it's the last time you'll ever see it. Will you come see it? In Korea, we say magpies bring good luck. I dreamt of one the last night I slept well. Though you are my daughter, I feel like a child. In our language, the word for cancer comes from the character for mouth. The fruit you bought is too tough to swallow. The cough is worse in the mornings and after rain. When you were younger, you loved the rain. If I could do anything, I would like to see the snow. To see it for the first time again, the cold a shivering afterthought. Time passes in pieces: one appointment, then the next. Monday, can you ask the doctor about the prescription? Will it be stronger? Every new day is an empty one. No appetite. No warmth. I hope I did not give you a rotten body, my body. Will I be stronger? I feel a shattering inside. Hello? You are breaking up. Remember to eat well, daughter. Remember to call home. Dr. Mikkael Sekeres: Hello and welcome to JCO's Cancer Stories: The Art of Oncology, which features essays and personal reflections from authors exploring their experience in the oncology field. I'm your host, Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. Today we are joined by Elane Kim, a student at Harvard College. In this episode, we will be discussing her Art of Oncology poem, “Transcription: Phone Call 2018.” At the time of this recording, our guest has no disclosures. Elane, what a joy to have you on our podcast. Welcome and thank you for joining us. Elane Kim: Thank you so much for having me - very excited. Dr. Mikkael Sekeres: So am I actually. Elane, I was wondering, I think you may be one of the youngest authors we've accepted a piece from. You had an absolutely gorgeous poem that you submitted to us and we were so thrilled that you chose us for your submission and ultimately that we were able to publish it. Elane Kim: Oh, that's so exciting. Dr. Mikkael Sekeres: So, can we start out with just kind of some general questions about you? Can you tell us about yourself? Where are you from? And walk us through how you reached this point in your career. Elane Kim: I'm originally from California, but I moved to the East Coast for college and I'm also a writer. I love to write fiction and poetry. When I first started writing, I wrote for fun for a really long time, but I started to kind of take it seriously in middle school because I went to this one slam poetry event and I remember I went home and I told my mom, “I am going to be a poet.” And so ever since then, I've been writing poetry and it's been really awesome for me because it's my way of expressing myself and translating my world into words and having a space where I'm able to experiment fearlessly. So I love to write and it's been a journey for me because I started publishing little poems here and there. And now my debut full length is coming out early next year with a small and lovely press. So I'm very excited and also honored to be on this podcast with you. Dr. Mikkael Sekeres: Elane, I can tell you as a parent of a daughter who's a rising senior in college, it's every parent's dream when your child comes home and says, “I want to be a poet.” So the question I wanted to ask is, are you a writer who dipped her toe into medicine or are you an aspiring doctor who dipped her toe into writing? Elane Kim: Oh my gosh, it's hard to say. I really love science, but I also really love writing. So I think maybe it comes from a place of wanting to do both because I also think that, I don't know, I really, really admire doctors for everything they do because from everything I've seen, I feel like medicine is a place where I think you need to have very deep empathy in order to proceed. So I also think writing is a place where you need empathy and so I think maybe a little bit of both. It's sort of hard for me to see which angle. Dr. Mikkael Sekeres: That's okay. You still have a couple years in college and, of course, the rest of your life to figure that out. But I think you're right. We obviously meet a lot of doctors who are writers. That's probably the main phenotype of the sort of person who submits something to the Art of Oncology at JCO. But I've always felt there's a lot of overlap between the two because inherently medicine is about storytelling. A patient comes to us with a story of illness. We tell that story to ourselves, to our colleagues when we're getting consults, and eventually we're trying to find the denouement of that story, where we have an answer for the story of illness. So I think it's great that you're still open to both aspects of this, writing and medicine, and I completely agree with you. I do think there's a lot of overlap between the two. Elane Kim: I think that's really beautiful. Dr. Mikkael Sekeres: Tell us about your journey as a writer then. So you talked about going to a poetry slam, but of course, you had to have gone there with a piece of poetry to participate. So when did you start writing poetry? Elane Kim: I always wrote poetry for fun. I loved making cards and stuff for my parents and my family for every little event. So I was my own like Hallmark factory. So I used to write really silly things and so whenever like people wanted cards or anything, I always had a poem ready. But then I started taking it seriously after this slam poetry event. I feel like slam poetry is very rooted in emotion and performance. And so all the poets there are so awesome and they really like are able to get into character and share their story in a very like raw way, which I thought was so, so awesome. And it was sort of the first time I had seen poetry as less of a vehicle for like a Valentine's Day joke or something and more of an actual story with like a punchline with a lot of character and individuality. And so that was sort of a space where I saw all these poets who were so excited about what they were doing and able to tell a story about something bigger than themselves. And so I think that was kind of a turning point and little middle school me, I was like, “This is totally what I want to do and totally something I want to pursue.” And although I no longer am like strictly in the spoken word space, I still think every single poem should be read aloud and should be shared with people in a space where everyone's listening and everyone's able to gain something new from it. Dr. Mikkael Sekeres: It's beautifully stated. And you know, that notion of reading words aloud is so important and that's advice that I give to some of my mentees even in scientific writing. As they're moving along, I'll actually say to them, “Okay, now read that paragraph or those sentences out loud and tell me if they make sense.” And as they're reading them, they'll often realize, “Wait a second, it's constructed the wrong way. And I'm burying the lead or the grammar doesn't quite work out.” And they rewrite it. So I love the fact that you talk about writing as something that should be read out loud. I think that's true whether you're writing creatively with poems or narrative pieces or even in scientific writing. Can you tell us what prompted you to write “Transcription: Phone Call 2018?” Elane Kim: Kind of like the title suggests, I wrote this poem after I had a phone call with a loved one that really stayed with me because I think there were a lot of, I guess, distances that were traversed through that phone call and it was a little bit more about what was left unsaid as opposed to what was said. So the poem is- it kind of addresses this, but there are language barriers, generational gaps, and also like the weight of illness that's bearing on this conversation that sort of bleeds into everyday life. And so I was thinking a little bit about how people can often carry conversations across physical distance and also emotional distance, especially in immigrant families, for example, where a lot of the times communication is something more emotional or cultural rather than something that's, you know, said through sentences. And so I think that the poem is both like a literal transcription of a phone call that's like spliced up, but also maybe like an emotional transcription where we're trying to preserve this moment of love and tenderness between a mother and a daughter. Dr. Mikkael Sekeres: It's really a terrific piece. I keep saying this over and over again. You captured so much in so few words, which of course, is the goal of poetry. One of the things that I loved about your poem is how you captured the fractured nature of phone calls, particularly if you're hearing bits and pieces on either side of the phone call. You start the poem focusing on otherness. I mean, right out of the gates, on being an outsider. Your first line is “Spiculated mass, irregular contours,” which is some of our medical speak. And then the next line immediately says, “Can you translate these words?” You're already saying the person, the character who's speaking that line doesn't get it, right? It doesn't make sense to them. They need help in figuring it out. Can you talk about this from the perspective of coming from another country or culture and as a neophyte to medical terminology? Elane Kim: Definitely. It's so awesome that you're able to notice all these small details and everything. That's so awesome. Dr. Mikkael Sekeres: It's a testimony to your writing. You're a great writer. Elane Kim: That's so kind of you, but I'm very excited to get to talk about all this. Yeah, like you said, there's like an insider/outsider dynamic. I guess as somebody who might be new to this country, there's also somebody who's new to medicine and how there can be a lot of barriers there where if you don't have somebody who's acting as somebody who can be in both worlds at once and translate these things, then you're sort of left in the dark. And I think the role of translator is very important here because you're not totally in one world or the other. You're kind of this floating being who is in charge of traversing both worlds and bringing, in this case, the mother from one to the next. But because of this, I think that sort of suggests that the person who is receiving the phone call is not totally comfortable in one world or the other world. They're sort of playing this mediator role. And I think that also maybe speaks to belonging in this poem as well. Dr. Mikkael Sekeres: Yeah. It really emphasizes how critical it is, particularly with serious diagnoses in medicine like cancer, that people bring with them another set of ears, or sometimes we'll joke and we'll say they bring an ectopic brain with them, someone else who can listen because it's not only the medical terminology that people trip over, but like you say, it's the emotions of the diagnosis and how receptive people are to the information. So they need somebody else there as another source of truth and another advocate to ask the right questions and also make sure that what the patient is hearing is what's being said and vice versa. So, are there poets who've been particular influences on you and if I could ask, who and how? Elane Kim: When I was first starting out, I really appreciated slam poets and I still do. I love slam poets. I remember I would go home and watch YouTube videos like over and over of these poets performing their work. For example, I really love Sarah Kay. I also really love Hieu Minh Nguyen. Both of them, oh my gosh, so, so awesome. And I think they bring a lot of, especially Sarah Kay, she brings a lot of whimsy into her work and also a lot of naturalistic references and also like scientific references that you wouldn't necessarily expect. Like, she has this one poem about these birds called starlings and when they fly together, they fly in the big shape of another starling, which is really fascinating, but also very poetic. I listened to that. I was like, “Wait, that is so awesome that nature knows to do that.” So things like that, I think I take a lot of inspiration from whenever there's something I learn about in, say, like my bio class. I'm like, “Write that down, write that down.” Because I'm like, “Oh, that could be something I put in my next poem.” But I also really love a lot of Asian and Asian American writers who have been big inspirations to me. I really love Jenny Xie. She has a collection called Eye Level, which blows me away every time I see a poem from it. I also love Chen Chen. He has this one poem, “When I Grow Up I Want to Be a List of Further Possibilities,” and I love that poem. It was one of the first poems I really fell in love with. Dr. Mikkael Sekeres: You've given me and our listeners a list of people to look up and to read. It's great. I'm curious about your writing process. What triggers a poem and how do you face the dreaded blank page on your computer? Elane Kim: So the way you avoid that is you never have it for too long. My method of writing, tried and true, is I have this one document where I collect everything and it's like my scraps and even the most random, like, ‘this would never go in a poem' random like throwaway lines, I put them all in one ginormous document. I don't know what I'm going to do if I lose access to it, to be honest, because it's like many, many pages. Basically, I just collect everything there. Like I will be in class and I will hear someone say something that's like just in a conversation, but I'm like, “Wait, that's kind of poetic.” And I write it down or like walking down the street and I'm looking at the water. I'm like, “Huh, that water looks a lot like this.” And I write that down. And so I have this huge, huge running document that has all these random lines. And so for me, I think writing is less about going into a document and like just type, type, type, type. It's more about for me like, how can I take these fragments and put them into a story? Like these random fragments. How can I tell a story out of these pieces that seem disparate initially? For me, I don't have a blank page for too long. My issue is like, how can I make this random mess of words into something that actually tells a story? But I think that's the most fun part of writing also is like putting together this puzzle. Dr. Mikkael Sekeres: I have to say it's also the most fun part of medicine. We're handed chaos in oncology and we're asked to put it together into a story and hopefully a story with a happy ending. So that's great. Elane Kim: I love that. Dr. Mikkael Sekeres: So you're welcome to write that down in your scraps. Elane Kim: Oh my gosh, it's going in there. Dr. Mikkael Sekeres: So, I wanted to end by actually quoting the end of your poem, which was amazing. And the poem reads like this and one of the characters says, “I feel a shattering inside. Hello? You're breaking up. Remember to eat well, daughter. Remember to call home.” And it's a marvelous, marvelously unsettling ending where both the phone call and the character are breaking up, while the character maintains her concern for her daughter. Do you think she's retaining some control of a cancer that obviously has gone beyond her control by expressing her maternal concerns about her daughter's welfare? Elane Kim: Definitely. I think this poem is a lot about how the mother experiences this loss of control. I think there's a moment where the mother and daughter sort of switch roles during the process of her care. She talks about how she starts to feel like a child again or she starts to feel less like a mother and more like the daughter. But I think at the end of the day, the way she expresses her care for her daughter is the way that she always has through like these small gestures. No matter how sick she is, her first concern is always her daughter and whether, you know, she's getting her meals in and just hearing her voice over the phone is something that she looks forward to. And so I think being able to like put somebody else above yourself even when your body is at its most sick is something that, I don't know, I think I find it very sad, but also I think a lot of mothers would also relate to putting your child above other things in moments of illness. And so I think it's a very poignant moment, but also, yeah, one that kind of rings true. Dr. Mikkael Sekeres: It's a poignant moment in an extremely poignant poem and beautifully written. We've been talking to Elane Kim about her poem, “Transcription: Phone Call 2018.” Elane, I want to thank you so much for joining us today. You are so incredibly accomplished and I can't wait to read all of your future pieces as well. Elane Kim: Oh, thank you so much. Narrator: Until next time, thank you for listening to JCO's Cancer Stories, The Art of Oncology. Don't forget to give us a rating or review or follow us and be sure to subscribe so you never miss an episode. You can find all of ASCO's shows at asco.org/podcasts. Until next time, thanks for joining us. 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. Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Elane Kim is a student at Harvard College.

S1 Ep167: Practice-Changing Lung Cancer Data From The 2025 ASCO Annual Meeting

Play Episode Listen Later Jun 23, 2025 45:29

In the wake of the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® put together an X Spaces discussion hosted by Stephen Liu, MD, and Joshua Sabari, MD, to highlight the most intriguing and practice-changing lung cancer abstracts. Discussed topics ranged from long-term follow-up with commonplace therapies to an analysis of what time of day is the best to administer immunochemotherapy. Liu, an associate professor of Medicine at Georgetown University, and the director of Thoracic Oncology and head of Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, and Sabari, an assistant professor in the Department of Medicine at the NYU Grossman School of Medicine, and the director of High Reliability Organization Initiatives at the Perlmutter Cancer Center, shared expert insights on the latest non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) breakthroughs. Trials of note that they discussed included: The phase 3 DeLLphi-304 trial (NCT05740566) - Tarlatamab (Imdelltra) versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304.1 The phase 3 IMforte trial (NCT05091567) - Lurbinectedin (Zepzelca; lurbi) + atezolizumab (Tecentriq; atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial.2 The phase 3 CheckMate 816 trial (NCT02998528) - Overall survival with neoadjuvant nivolumab (Opdivo; NIVO) + chemotherapy (chemo) in patients with resectable NSCLC in CheckMate 816.3 The phase 3 PACIFIC15 trial (NCT05549037) - Randomized trial of relevance of time-of-day of immunochemotherapy for progression-free and overall survival in patients with non–small cell lung cancer.4 The phase 3 Beamion LUNG-1 trial (NCT04886804) - Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non–small cell lung cancer (NSCLC): results from the Beamion LUNG-1 trial.5 The phase 3 ARTEMIA trial (NCT06472245) - Phase 3 trial of the therapeutic cancer vaccine OSE2101 versus docetaxel in patients with metastatic non–small cell lung cancer and secondary resistance to immunotherapy. References Rudin C, Mountzios G, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304. J Clin Oncol. 2025;43(suppl 17):LBA8008. doi:10.1200/JCO.2025.43.17_suppl.LBA8008 Paz-Ares L, Borghaei H, Liu SV, et al. Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial. J Clin Oncol. 2025;43(suppl 16):8006. doi:10.1200/JCO.2025.43.16_suppl.8006 Forde PM, Spicer JD, Provencio M, et al. Overall survival with neoadjuvant nivolumab + chemotherapy in patients with resectable NSCLC in CheckMate 816. J Clin Oncol. 2025;43(suppl 17):LBA8000. doi:10.1200/JCO.2025.43.17_suppl.LBA8000 Zhang Y, Huang Z, Zeng L, et al. Randomized trial of relevance of time-of-day of immunochemotherapy for progression-free and overall survival in patients with non-small cell lung cancer. J Clin Oncol. 2025;43(suppl 16):8516. doi:10.1200/JCO.2025.43.16_suppl.8516 Sabari JK, Nadal E, Hendriks L, et al. Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC): results from the Beamion LUNG-1 trial. J Clin Oncol. 2025;43(suppl 16):8620. doi:10.1200/JCO.2025.43.16_suppl.8620 Liu SV, Guibert C, Tostivint EP, et al. Phase 3 trial of the therapeutic cancer vaccine OSE2101 versus docetaxel in patients with metastatic non-small cell lung cancer and secondary resistance to immunotherapy. J Clin Oncol. 2025;43(suppl 16):TPS8651. doi:10.1200/JCO.2025.43.16_suppl.TPS8651

CAR T and Transplantation Advances Across Hematologic Cancers at ASCO 2025

ASTCT Talks

Play Episode Listen Later Jun 16, 2025 35:19

An expert panel highlights key presentations in multiplemyeloma, lymphoma, and other hematologic malignancies at the 2025 ASCO Annual Meeting.CancerNetwork®, in collaboration with The American Societyfor Transplantation and Cellular Therapy (ASTCT), organized an X Space hosted by Rahul Banerjee, MD, FACP; Taha Al-Juhaishi, MD; and Muhammad Salman Faisal, MD. This expert panel convened to discuss key presentations and abstracts of interest at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting featuring noteworthy developments in modalities like CAR T-cell therapy and transplantation across multiple myeloma, lymphoma, and other disease types.Banerjee is an assistant professor in the Clinical Research Division at the Fred Hutchinson Cancer Center in Seattle, Washington. Al-Juhaishi is the associate director of the Hematopoietic Stem Cell Transplantation and Cell Therapy Program at Oklahoma University Health Stephenson Cancer Center and an assistant professor of medicine at the University of Oklahoma College of Medicine. Faisal is a hematologist/oncologist at Oklahoma University HealthStephenson Cancer Center and serves as an ambassador for ASCO.The group highlighted several late-breaking abstracts,plenary sessions, and poster presentations focused on significant clinical trial data and other findings across the hematologic oncology landscape. Topics of interest included the following:Phase 1b/2 CARTITUDE-1 trial (NCT03548207,NCT05201781)1Long-term follow-up showed that approximately one-third(33%; n = 32) of patients with relapsed/refractory multiple myeloma maintained progression-free status for at least 5 years following a single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti). An equal likelihood of progression-free survival occurred in patients with high-risk cytogenetics or extramedullary plasmacytomas.With a median follow-up of 61.3 months, the median overall survival (OS) with cilta-cel was 60.7 months (95% CI, 41.9-notevaluable [NE]). Real-world axicabtagene ciloleucel (axi-cel; Yescarta) use2Across inpatient and outpatient treatment settings, safety and efficacy outcomes were comparable for patients who received axi-cel for relapsed/refractory large B-cell lymphoma.Multivariate analysis showed no associations between intended care setting and cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.Investigators noted that these real-world data support the consideration of axi-cel in appropriate outpatient settings.Phase 1b/2 NEXICART-2 trial (NCT06097832)3Investigators assessed NXC-201, a sterically optimized CAR T construct, as a treatment for patients with relapsed/refractory light chain amyloidosis, a population with no FDA-approved options.Among 12 patients who received the agent at 450x 106 cells, 100% achieved rapid and deep hematologic responses at a median time to first and best response of 7 and 26 days, respectively. With a median follow-up of 121 days (range, 29-289), no hematologic relapses or progression had occurred.References1. Voorhees P, Martin T, Lin Y, et al. Long-term (≥5 year) remission and survival after treatment with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2025;43(suppl 16):7507. doi: 10.1200/JCO.2025.43.16_suppl.75072. Furqan F, Hemmer M, Tees M, et al. Trends and outcomes by inpatient and outpatient infusion of axicabtagene ciloleucel (axi-cel) in the US for patients (pts) with relapsed/refractory large B-celllymphoma (R/R LBCL). J Clin Oncol. 2025;43(suppl 16):7023. doi:10.1200/JCO.2025.43.16_suppl.70233. Landau H, Hughes C, Rosenberg A, et al. Safety and efficacy data from Nexicart-2, the first US trial of CAR-T in R/R light chain (AL) amyloidosis, Nxc-201. J Clin Oncol. 2025;43(suppl 16):7508.doi:10.1200/JCO.2025.43.16_suppl.7508

university washington real seattle medicine safety cancer md os phase fda cart advances american society investigators rr faisal asco transplantation banerjee oklahoma college asco annual meeting jco multivariate hematologic martin t j clin oncol clinical oncology asco annual meeting clinical research division rahul banerjee nxc

A Whipple of Choice: Choosing Between Debilitating Surgery or Watchful Waiting

Play Episode Listen Later Jun 10, 2025 30:02

Listen to ASCO's Journal of Clinical Oncology Art of Oncology article, "A Whipple of Choice” by Dr. Carl Forsberg, who is an Assistant Professor of Strategy and History at Air Force War College. The article is followed by an interview with Forsberg and host Dr. Mikkael Sekeres. Dr Forsberg shares his experience with an uncommon cancer treated by a new therapy for which no directly relevant data were available. Transcript Narrator: A Whipple of Choice, by C. W. Forsberg, PDH I sat across from a hepatobiliary surgeon on a gray October afternoon. “To be frank,” he told me, “we don't know what to recommend in your case. So we default to being conservative. That means a Whipple surgery, even though there are no data showing it will improve your outcome.” The assessment surprised me, diverging from my expectation that doctors provide clear recommendations. Yet the surgeon's willingness to structure our conversation around the ambiguity of the case was immensely clarifying. With a few words he cut through the frustrations that had characterized previous discussions with other physicians. I grasped that with an uncommon cancer treated by a novel therapy with no directly relevant data, I faced a radical choice. My situation that afternoon was worlds away from where I was 5 months earlier, when I was diagnosed with presumed pancreatic cancer at the age of 35. An early scan was suspicious for peritoneal metastasis. The implications seemed obvious. I prepared myself for the inevitable, facing my fate stoically except in those moments when I lingered next to my young son and daughter as they drifted to sleep. Contemplating my death when they were still so vulnerable, I wept. Then the specter of death retreated. Further tests revealed no metastasis. New doctors believed the tumor was duodenal and not pancreatic. More importantly, the tumor tested as deficient mismatch repair (dMMR), predictable in a Lynch syndrome carrier like me. In the 7 years since I was treated for an earlier colon cancer, immune checkpoint inhibitor (ICI) immunotherapy had revolutionized treatment of dMMR and high microsatellite instability tumors. One oncologist walked me through a series of recent studies that showed extraordinary responses to ICI therapy in locally advanced colon and rectal tumors with these biomarkers.1-4 He expressed optimism that my cancer could have a similar response. I embarked on a 24-week course of nivolumab and ipilimumab. After 6 weeks of therapy, a computed tomography (CT) scan showed a significant reduction in tumor size. My health rebounded as the tumor receded. This miraculous escape, however, was bound by the specter of a Whipple surgery, vaguely promised 6 months into my treatment. At the internationally renowned center where I was diagnosed and began treatment with astonishing efficiency, neither oncologists nor surgeons entertained the possibility of a surgery-sparing approach. “In a young, healthy patient like you we would absolutely recommend a Whipple,” my first oncologist told me. A second oncologist repeated that assessment. When asked if immunotherapy could provide a definitive cure, he replied that “if the tumor disappeared we could have that conversation.” My charismatic surgeon exuded confidence that I would sail through the procedure: “You are in excellent health and fitness—it will be a delicious surgery for me.” Momentum carried me forward in the belief that surgery was out of my hands. Four months into treatment, I was jolted into the realization that a Whipple was a choice. I transferred my infusions to a cancer center nearer my home, where I saw a third oncologist, who was nearly my age. On a sunny afternoon, 2 months into our relationship, he suggested I think about a watch-and-wait approach that continued ICI therapy with the aim of avoiding surgery. “Is that an option?” I asked, taken aback. “This is a life-changing surgery,” he responded. “You should consider it.” He arranged a meeting for me with his colleague, the hepatobiliary surgeon who clarified that “there are no data showing that surgery will improve your outcome.” How should patients and physicians make decisions in the absence of data? My previous experience with cancer offered little help. When I was diagnosed with colon cancer at the age of 28, doctors made clear recommendations based on clear evidence. I marched through surgery and never second-guessed my choices. A watch-and-wait approach made sense to me based on theory and extrapolation. Could duodenal tumors treated by ICIs behave that differently from colorectal cancers, for which data existed to make a watch-and-wait approach appear reasonable? The hepatobiliary surgeon at the regional cancer center told me, “I could make a theoretical argument either way and leave you walking out of here convinced. But we simply don't know.” His comment reflects modern medicine's strict empiricism, but it foreclosed further discussion of the scientific questions involved and pushed the decision into the realm of personal values. Facing this dilemma, my family situation drove me toward surgery despite my intuition that immunotherapy could provide a definitive cure. The night before I scheduled my Whipple procedure, I wrote in my journal that “in the face of radical uncertainty one must resort to basic values—and my priority is to survive for my children. A maimed, weakened father is without doubt better than no father at all.” To be sure, these last lines were written with some bravado. Only after the surgery did I viscerally grasp that the Whipple was a permanent maiming of the GI system. My doubts lingered after I scheduled surgery, and I had a final conversation with the young oncologist at the cancer center near my home. We discussed a watch-and-wait approach. A small mass remained on CT scans, but that was common even when tumors achieved a pathological complete response.5 Another positron emission tomography scan could provide more information but could not rule out the persistence of lingering cancer cells. I expressed my low risk tolerance given my personal circumstances. We sat across from one another, two fathers with young children. My oncologist was expecting his second child in a week. He was silent for moments before responding “I would recommend surgery in your situation.” Perhaps I was projecting, but I felt the two of us were in the same situation: both wanting a watch-and-wait approach, both intuitively believing in it, but both held back by a sense of parental responsibility. My post-surgery pathology revealed a pathological complete response. CT scans and circulating tumor DNA tests in the past year have shown no evidence of disease. This is an exceptional outcome. Yet in the year since my Whipple, I have been sickened by my lack of gratitude for my good fortune, driven by a difficult recovery and a sense that my surgery had been superfluous. Following surgery, I faced complications of which I had been warned, such as a pancreatic fistula, delayed gastric emptying, and pancreatic enzyme insufficiency. There were still more problems that I did not anticipate, including, among others, stenoses of arteries and veins due to intraabdominal hematomas, persistent anemia, and the loss of 25% of my body weight. Collectively, they added up to an enduringly dysfunctional GI system and a lingering frailty. I was particularly embittered to have chosen surgery to mitigate the risk that my children would lose their father, only to find that surgery prevented me from being the robust father I once was. Of course, had I deferred surgery and seen the tumor grow inoperable or metastasize between scans, my remorse would have been incalculably deeper. But should medical decisions be based on contemplation of the most catastrophic consequences, whatever their likelihood? With hindsight, it became difficult not to re-examine the assumptions behind my decision. Too often, my dialogue with my doctors was impeded by the assumption that surgery was the obvious recommendation because I was young and healthy. The assumption that younger oncology patients necessarily warrant more radical treatment deserves reassessment. While younger patients have more years of life to lose from cancer, they also have more years to deal with the enduring medical, personal, and professional consequences of a life-changing surgery. It was not my youth that led me to choose surgery but my family situation: 10 years earlier, my youth likely would have led me to a watch-and-wait approach. The rising incidence of cancer among patients in their 20s and 30s highlights the need for a nuanced approach to this demographic. Calculations on surgery versus a watch-and-wait approach in cases like mine, where there are no data showing that surgery improves outcomes, also require doctors and patients to account holistically for the severity of the surgery involved. Multiple surgeons discussed the immediate postsurgical risks and complications of a pancreaticoduodenectomy, but not the long-term challenges involved. When asked to compare the difficulty of my prior subtotal colectomy with that of a pancreatoduodenectomy, the surgeon who performed my procedure suggested they might be similar. The surgeon at the regional cancer center stated that the Whipple would be far more difficult. I mentally split the difference. The later assessment was right, and mine was not a particularly bad recovery compared with others I know. Having been through both procedures, I would repeat the subtotal colectomy for a theoretical oncologic benefit but would accept some calculated risk to avoid a Whipple. Most Whipple survivors do not have the privilege of asking whether their surgery was necessary. Many celebrate every anniversary of the procedure as one more year that they are alive against the odds. That I can question the need for my surgery speaks to the revolutionary transformation which immunotherapy has brought about for a small subset of patients with cancer. The long-term medical and personal consequences of surgery highlight the urgent stakes of fully understanding and harnessing the life-affirming potential of this technology. In the meantime, while the field accumulates more data, potentially thousands of patients and their physicians will face difficult decisions on surgery verses a watch and- wait approach in cases of GI tumors with particular biomarkers showing exceptional responses to ICI therapy.7,8 Under these circumstances, I hope that all patients can have effective and transparent conversations with their physicians that allow informed choices accounting for their risk tolerance, calculations of proportionality, and priorities. Dr. Mikkael Sekeres: Hello, and welcome to JCO's Cancer Stories: The Art of Oncology, which features essays and personal reflections from authors exploring their experience in the oncology field. I'm your host, Dr. Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center at University of Miami. Today, we are so happy to be joined by Dr. Carl Forsberg, Assistant Professor of Strategy and History at the Air Force War College. In this episode, we will be discussing his Art of Oncology article, "A Whipple of Choice." At the time of this recording, our guest has no disclosures. Carl, it is such a thrill to welcome you to our podcast, and thank you for joining us. Dr. Carl Forsberg: Well, thank you, Mikkael, for having me. I'm looking forward to our conversation. Dr. Mikkael Sekeres: So am I. I wanted to start, Carl, with just a little bit of background about you. It's not often we have a historian from the Air Force College who's on this podcast. Can you tell us about yourself, where you're from, and walk us through your career? Dr. Carl Forsberg: Sure. I was born and raised in Minnesota in a suburb of Minneapolis-St. Paul and then went to undergraduate on the East Coast. I actually started my career working on the contemporary war in Afghanistan, first as an analyst at a DC think tank and then spent a year in Kabul, Afghanistan, on the staff of the four-star NATO US headquarters, where I worked on the vexing problems of Afghanistan's dysfunctional government and corruption. Needless to say, we didn't solve that problem. Dr. Mikkael Sekeres: Wow. Dr. Carl Forsberg: I returned from Afghanistan somewhat disillusioned with working in policy, so I moved into academia, did a PhD in history at the University of Texas at Austin, followed by postdoctoral fellowships at Harvard and Yale, and then started my current position here at the Air Force War College. The War Colleges are, I think, somewhat unusual, unique institutions. Essentially, we offer a 1-year master's degree in strategic studies for lieutenant colonels and colonels in the various US military services. Which is to say my students are generally in their 40s. They've had about 20 years of military experience. They're moving from the operational managerial levels of command to positions where they'll be making strategic decisions or be strategic advisors. So we teach military history, strategy, international relations, national security policy to facilitate that transition to a different level of thinking. It really is a wonderful, interesting, stimulating environment to be in and to teach in. So I've enjoyed this position here at the War College quite a lot. Dr. Mikkael Sekeres: Well, I have to tell you, as someone who's been steeped in academic medicine, it sounds absolutely fascinating and something that I wouldn't even know where to start approaching. We have postdoctoral fellowships, of course, in science as well. What do you do during a postdoctoral fellowship in history and strategy? Dr. Carl Forsberg: It's often, especially as a historian, it's an opportunity to take your dissertation and expand it into a book manuscript. So you have a lot of flexibility, which is great. And, of course, a collegial environment with others working in similar fields. There are probably some similarities to a postdoc in medicine in terms of having working groups and conferences and discussing works in progress. So it was a great experience for me. My second postdoc occurred during the pandemic, so it turned out to be an online postdoc, a somewhat disappointing experience, but nevertheless I got a lot out of the connections and relationships I formed during those two different fellowships. Dr. Mikkael Sekeres: Well, there are some people who used the pandemic as an excuse to really just plow into their writing and get immersed in it. I certainly wrote one book during the pandemic because I thought, “Why not? I'm home. It's something where I can use my brain and expand my knowledge base.” So I imagine it must have been somewhat similar for you as you're thinking about expanding your thesis and going down different research avenues. Dr. Carl Forsberg: I think I was less productive than I might have hoped. Part of it was we had a 2-year-old child at home, so my wife and I trying to, you know, both work remotely with a child without having childcare really for much of that year given the childcare options fell through. And it was perhaps less productive than I would have aspired for it to be. Dr. Mikkael Sekeres: It's terrifically challenging having young children at home during the pandemic and also trying to work remotely with them at home. I'm curious, you are a writer, it's part of your career, and I'm curious about your writing process. What triggers you to write a story like you did, and how does it differ from some of your academic writing? Dr. Carl Forsberg: Yeah. Well, as you say, there is a real difference between writing history as an academic and writing this particular piece. For me, for writing history, my day job, if you will, it's a somewhat slow, painstaking process. There's a considerable amount of reading and archival work that go into history. I'm certainly very tied to my sources and documents. So, you know, trying to get that precision, making sure you've captured a huge range of archival resources. The real narrative of events is a slow process. I also have a bad habit of writing twice as much as I have room for. So my process entailed a lot of extensive revisions and rewriting, both to kind of shorten, to make sure there is a compelling narrative, and get rid of the chaff. But also, I think that process of revision for me is where I often draw some of the bigger, more interesting conclusions in my work once I've kind of laid out that basis of the actual history. Certainly, writing this article, this medical humanities article, was a very different experience for me. I've never written something about myself for publication. And, of course, it was really driven by my own experiences of going through this cancer journey and recovering from Whipple surgery as well. The article was born during my recovery, about 4 months after my Whipple procedure. It was a difficult time. Obviously kind of in a bad place physically and, in my case, somewhat mentally, including the effects of bad anemia, which developed after the surgery. I found it wasn't really conducive to writing history, so I set that aside for a while. But I also found myself just fixating on this question of had I chosen a superfluous Whipple surgery. I think to some extent, humans can endure almost any suffering with a sense of purpose, but when there's a perceived pointlessness to the suffering, it makes it much harder. So for me, writing this article really was an exercise, almost a therapeutic one, in thinking through the decisions that led me to my surgery, addressing my own fixation on this question of had I made a mistake in choosing to have surgery and working through that process in a systematic way was very helpful for me. But it also, I think, gave me- I undertook this with some sense of perhaps my experience could be worthwhile and helpful for others who would find themselves in a situation like mine. So I did write it with an eye towards what would I like to have read? What would I like to have had as perspective from another patient as I grappled with the decision that I talk about in the article of getting a Whipple surgery. Dr. Mikkael Sekeres: So I wonder if I could back up a little bit. You talk about the difficulty of undergoing a Whipple procedure and of recovery afterwards, a process that took months. And this may come across as a really naive question, but as, you know, as an oncologist, my specialty is leukemia, so I'm not referring people for major surgeries, but I am referring them for major chemotherapy and sometimes to undergo a bone marrow transplant. Can you educate us what makes it so hard? Why was it so hard getting a Whipple procedure, and what was hard about the recovery? Dr. Carl Forsberg: Yeah, it was a long process. Initially, it was a 14-day stay in the hospital. I had a leaking pancreas, which my understanding is more common actually with young, healthy patients just because the pancreas is softer and more tender. So just, you know, vast amount of pancreatic fluid collecting in the abdominal cavity, which is never a pleasant experience. I had a surgical drain for 50-something days, spent 2 weeks in the hospital. Simply eating is a huge challenge after Whipple surgery. I had delayed gastric emptying for a while afterwards. You can only eat very small meals. Even small meals would give me considerable stomach pain. I ended up losing 40 lb of weight in 6 weeks after my surgery. Interestingly enough, I think I went into the surgery in about the best shape I had been in in the last decade. My surgeon told me one of the best predictors for outcomes is actual muscle mass and told me to work out for 2 hours every day leading up to my surgery, which was great because I could tell my wife, "Sorry, I'm going to be late for dinner tonight. I might die on the operating table." You can't really argue with that justification. So I went in in spectacular shape and then in 6 weeks kind of lost all of that muscle mass and all of the the strength I had built up, which just something discouraging about that. But just simply getting back to eating was an extraordinarily difficult process, kind of the process of trial and error, what worked with my system, what I could eat without getting bad stomach pains afterwards. I had an incident of C. diff, a C. diff infection just 5 weeks after the surgery, which was obviously challenging. Dr. Mikkael Sekeres: Yeah. Was it more the pain from the procedure, the time spent in the hospital, or psychologically was it harder? Dr. Carl Forsberg: In the beginning, it was certainly the physical elements of it, the difficulty eating, the weakness that comes with losing that much weight so quickly. I ended up also developing anemia starting about two or 3 months in, which I think also kind of has certain mental effects. My hemoglobin got down to eight, and we caught it somewhat belatedly. But I think after about three or 4 months, some of the challenges became more psychological. So I started to physically recover, questions about going forward, how much am I going to actually recover normal metabolism, normal gastrointestinal processes, a question of, you know, what impact would this have long-term. And then, as I mentioned as well, some of the psychological questions of, especially once I discovered I had a complete pathological response to the immunotherapy, what was the point to having this surgery? Dr. Mikkael Sekeres: And the way you explore this and revisit it in the essay is absolutely fascinating. I wanted to start at the- towards the earlier part of your essay, you write, "The surgeon's willingness to structure our conversation around the ambiguity of the case was immensely clarifying." It's fascinating. The ambiguity was clarifying to you. And the fact that you appreciated the fact that the surgeon was open to talking about this ambiguity. When do you think it's the right thing to acknowledge ambiguity in medicine, and when should we be more definitive? When do you just want someone to tell you, “Do this or do that?” Dr. Carl Forsberg: That's a great question, which I've thought about some. I think some of it is, I really appreciated the one- a couple of the oncologists who brought up the ambiguity, did it not at the beginning of the process but a few months in. You know, the first few months, you're so as a patient kind of wrapped up in trying to figure out what's going on. You want answers. And my initial instinct was, you know, I wanted surgery as fast as possible because you want to get the tumor out, obviously. And so I think bringing up the ambiguity at a certain point in the process was really helpful. I imagine that some of this has to do with the patient. I'm sure for oncologists and physicians, it's got to be a real challenge assessing what your patient wants, how much they want a clear answer versus how much they want ambiguity. I've never obviously been in the position of being a physician. As a professor, you get the interesting- you start to realize some students want you to give them answers and some students really want to discuss the ambiguities and the challenges of a case. And so I'm, I imagine it might be similar as a physician, kind of trying to read the patient. I guess in my case, the fact was that it was an extraordinarily ambiguous decision in which there wasn't data. So I think there is an element, if the data gives no clear answers, that I suppose there's sort of an ethical necessity of bringing that up with the patient. Though I know that some patients will be more receptive than others to delving into that ambiguity. Dr. Mikkael Sekeres: Well, you know, it's an opportunity for us to think holistically about our patients, and you as a patient to think holistically about your health and your family and how you make decisions. I believe that when we're in a gray zone in medicine where the data really don't help guide one decision versus the next, you then lean back towards other values that you have to help make that decision. You write beautifully about this. You say, "In the face of radical uncertainty, one must resort to basic values, and my priority is to survive for my children. A maimed, weakened father is without doubt better than no father at all." That's an incredibly deep sentiment. So, how do you think these types of decisions about treatment for cancer change over the course of our lives? You talk a lot about how you were a young father in this essay, and it was clear that that was, at least at some point, driving your decision. Dr. Carl Forsberg: Yeah, I certainly have spent a lot of time thinking about how I would have made this decision differently 10 years earlier. As I mentioned the article, it was interesting because most of my physicians, honestly, when they were discussing why surgery made sense pointed to my age. I don't think it was really my age. Actually, when I was 23, I went off to Afghanistan, took enormous risks. And to some extent, I think as a young single person in your 20s, you actually have generally a much higher risk tolerance. And I think in that same spirit, at a different, earlier, younger stage in my life, I would have probably actually been much more willing to accept that risk, which is kind of a point I try to make, is not necessarily your age that is really the deciding factor. And I think once again, if I were 70 or 60 and my children, you know, were off living their own lives, I think that also would have allowed me to take, um, greater risk and probably led me to go for a watch-and-wait approach instead. So there was a sense at which not the age, but the particular responsibilities one has in life, for me at least, figured very heavily into my medical calculus. Dr. Mikkael Sekeres: It's so interesting how you define a greater risk as watch and wait, whereas a surgeon or a medical oncologist who's making recommendations for you might have defined the greater risk to undergo major surgery. Dr. Carl Forsberg: And I thought about that some too, like why is it that I framed the watch and wait as a greater risk? Because there is a coherent case that actually the greater risk comes from surgery. I think when you're facing a life and death decision and the consequence, when you have cancer, of course, your mind goes immediately to the possibility of death, and that consequence seems so existential that I think it made watch and wait perhaps seem like the riskier course. But that might itself have been an assumption that needed more analysis. Dr. Mikkael Sekeres: Do you think that your doctor revealing that he also had young children at home helped you with this decision? Dr. Carl Forsberg: I think in some ways for a doctor it's important to kind of understand where your patient is in their own life. As a patient, it was interesting and always helpful for me to understand where my physicians were in their life, what was shaping their thinking about these questions. So I don't know if it in any way changed my decision-making, but it definitely was important for developing a relationship of trust as well with physicians that we could have that mutual exchange. I would consider one of my primary oncologists, almost something of a friend at this point. But I think it really was important to have that kind of two-way back and forth in understanding both where I was and where my physician was. Dr. Mikkael Sekeres: I like how you frame that in the sense of trust and hearing somebody who could make similar considerations to you given where he was in his family. One final question I wanted to ask you. You really elegantly at the end of this essay talk about revisiting the decision. I wonder, is it fair to revisit these types of decisions with hindsight, or do we lose sight of what loomed as being most important to us when we were making the decisions in real time? Dr. Carl Forsberg: That's a great question, one that is also, I think, inherent to my teaching. I teach military history for lieutenant colonels and colonels who very well may be required, God willing not, but may be required to make these sort of difficult decisions in the case of war. And we study with hindsight. But one thing I try to do as a professor is put them in the position of generals, presidents, who did not have the benefit of hindsight, trying to see the limits of their knowledge, use primary source documents, the actual memos, the records of meetings that were made as they grappled with uncertainty and the inherent fog of war. Because it is, of course, easy to judge these things in hindsight. So definitely, I kept reminding myself of that, that it's easy to second guess with hindsight. And so I think for me, part of this article was trying to go through, seeing where I was at the time, understanding that the decision I made, it made sense and with what I knew, it was probably the right decision, even if we can also with hindsight say, "Well, we've learned more, we have more data." A lot of historical leaders, it's easy to criticize them for decisions, but when you go put yourself in their position, see what the alternatives were, you start to realize these were really hard decisions, and I would have probably made the same disastrous mistake as they would have, you know. Let's just say the Vietnam War, we have our students work through with the original documents decisions of the Joint Chiefs in 1965. They very frequently come to the exact same conclusions as American policymakers made in 1965. It is a real risk making judgments purely on the basis of hindsight, and I think it is important to go back and really try to be authentic to what you knew at the time you made a decision. Dr. Mikkael Sekeres: What a great perspective on this from a historian. Carl Forsberg, I'd like to thank you, and all of us are grateful that you were willing to share your story with us in The Art of Oncology. Dr. Carl Forsberg: Well, thank you, and it's yeah, it's been a, it's a, I think in some ways a very interesting and fitting place to kind of end my cancer journey with the publication of this article, and it's definitely done a lot to help me work through this entire process of going through cancer. So, thank you. Dr. Mikkael Sekeres: Until next time, thank you for listening to JCO's Cancer Stories: The Art of Oncology. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all of ASCO's shows at asco.org/podcasts. Until next time, thank you so much. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show notes:Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr. Carl Forsberg is a Assistant Professor of Strategy and History at the Air Force War College.

JCO at ASCO Annual Meeting: Neoadjuvant Osimertinib for Resectable EGFR-Mutated NSCLC

Play Episode Listen Later Jun 2, 2025 6:54

JCO Editorial Fellow Dr. Ece Cali Daylan and JCO Associate Editor Dr. Thomas Stinchcombe discuss the ASCO 2025 Simultaneous Publication paper "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small-Cell Lung Cancer." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Ece Cali: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Ece Cali, JCO Editorial Fellow, and I am joined by JCO Associate Editor, Dr. Tom Stinchcombe. In this episode, we will discuss the Journal of Clinical Oncology article and abstract presentation "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer.” NeoADAURA is a randomized global phase III study investigating the efficacy of neoadjuvant osimertinib-containing regimens in patients with resectable EGFR-mutated stage II to IIIB non–small-cell lung cancer. 358 patients were randomized 1:1:1 to receive osimertinib plus chemotherapy, osimertinib monotherapy, or placebo plus chemotherapy in the neoadjuvant setting. The primary endpoint was major pathological response. Osimertinib plus chemotherapy and osimertinib alone demonstrated MPR rates of 26% and 25%, respectively, compared to 2% in the chemotherapy plus placebo arm with a p-value of less than 0.001. Tom, can you please explain to our listeners how you interpret this data? Dr. Thomas Stinchcombe: Great question. Yeah, I think to give a little context, obviously, chemotherapy and immunotherapies preoperatively is becoming the standard of care. However, patients with EGFR-mutant lung cancer generally have not responded to immunotherapy, and many of the trials excluded patients with known EGFR mutation. There have been smaller phase II trials that had looked at EGFR TKIs preoperatively, but none of these were definitive. So I think that this trial is a big trial, and I think some of the strengths are that it has osimertinib alone and chemotherapy with osimertinib arms as compared to the standard of chemotherapy. I think it's going to be really interesting at the meeting to see how this is discussed by the discussant and also what the reaction is to its public presentation. And I think that's largely because there's an alternative paradigm now, surgical resection adjuvant osimertinib, that's available to patients. So I think this will be interesting to see what the reaction is to the induction therapy. For patients with known N2 disease, I've generally given some form of induction therapy prior to surgical resection. So I think that's the subgroup of patients that I'm most likely to employ this approach with based on the results. Dr. Ece Cali: So, in this trial, more than 90% of the patients on the osimertinib-containing regimens underwent curative-intent surgery. So, this speaks to the feasibility of the approach, and the higher MPR rate with osimertinib-containing regimens is encouraging. Event-free survival data is currently immature. You have already touched upon some of the strengths of the trial, but what are the weaknesses and the strengths of this trial? Dr. Thomas Stinchcombe: So, I mean, I think there are some weaknesses. A major pathological response was chosen as an endpoint, and there could be an argument that path CR is more of a prognostic marker. However, the rates of path CR are relatively low, so it would have been very hard to design a trial such as that. And then I think the trial started off as a preoperative trial but effectively became a perioperative trial with preoperative EGFR-TKI, postoperative osimertinib. And so I think it's going to be very hard to determine what the contribution of the components are. And then you've hit on another part that I think is very important when we interpret the data that the maturity on the event-free survival is only 15%, and most people are still on therapy. So the event-free survival, which is an important endpoint, is very immature right now. Dr. Ece Cali: And this trial was designed to compare the neoadjuvant approaches, hence the comparator arm here is neoadjuvant chemotherapy followed by surgery. So, considering the ADAURA trial results with upfront surgery followed by osimertinib as adjuvant, so how do you see this trial's impact on the current clinical practice? Dr. Thomas Stinchcombe: Well, very good question, I think one that we're still struggling with as we kind of look at this data. I think, for me, stage II patients will most likely go to surgery and then get adjuvant osimertinib, and then maybe the N2 patients will get an osimertinib-containing regimen as an induction therapy. I think one of the questions is does it really matter when you get the osimertinib as long as you get it at some point? And I think that's going to be the critical interpretation of some of the data at this point. Dr. Ece Cali: And how do you think this trial shapes the future research for patients with resectable EGFR-mutated lung cancer? Dr. Thomas Stinchcombe: Well, I mean, I think it shows that chemotherapy was really modestly active with an MPR rate of 2%, no pathological responses. And then I think you're going to have to look at an osimertinib plus another targeted therapy component. I think, you know, when I looked at the osimertinib versus the chemo-osimertinib arm, I also was sort of surprised that the MPR rate and the path CR rate were very, very similar. So I think that the question is would a double targeted therapy approach or some other approach matter? And I think it also sets a safety standard. And you touched on this in your comments, that there was not a disparity in terms of the rate of going to surgery or R0/R1 resections. So patients were not having progressive disease events or toxicities that prevented surgery. So I think it does give us good safety data. Dr. Ece Cali: Tom, thank you so much for sharing your insights on the JCO article, "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting, and please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

event journal annual meetings asco egfr clinical oncology n2 mpr nsclc mutated neoadjuvant asco annual meeting jco iiib resectable osimertinib egfr tkis adaura egfr tki

Ep. 547 Intratumoral Oncolytic Treatments for Metastatic Melanoma: A Multidisciplinary Approach with Dr. Riad Salem and Dr. Sunandana Chandra

Play Episode Listen Later May 27, 2025 53:59

Making strides against melanoma: how can medical oncologists and interventional oncologists join forces to deliver smarter, patient-centered care? In this episode of BackTable, Dr. Tyler Sandow, hosts Dr. Sunandana Chandra, medical oncologist at Northwestern, and Dr. Riad Salem, interventional oncologist at Northwestern to discuss the evolving management of advanced melanoma. --- This podcast is supported by an educational grant from Replimune. --- SYNPOSIS The doctors open the episode with an overview of melanoma and recent advances in its treatment, highlighting key trials such as DREAMseq and CheckMate 067. The discussion explores the shift from medical oncologist as solo primary providers to a dynamic, multidisciplinary approach to advanced cancer care—emphasizing cutting-edge treatments like immunotherapy and intratumoral oncolytic viruses. Dr. Salem shares practical insights on the procedural techniques of administering intratumoral oncolytics like Replimune, emphasizing the importance of thorough documentation and patient-centered care. The doctors also provide an overview of the ongoing IGNYTE-3 Trial, a Phase 3 study assessing the safety and efficacy of the oncolytic immunotherapy RP1 in combination with nivolumab for the treatment of advanced melanoma. The episode underscores the transformative potential of innovative melanoma treatments and the crucial role of integrated, team-based approaches in improving cancer patient outcomes. --- TIMESTAMPS 00:00 - Introduction03:48 - The Evolution of Melanoma Treatment: From Chemotherapy to Immunotherapy14:05 - The Role of Oncolytic Viruses in Melanoma Treatment20:14 - Interventional Radiology's Role in Cancer Treatment27:00 - Collaborative Approach to Cancer Care32:53 - Hyper Documentation and Communication Efficiency44:47 - Future of Intratumoral Oncolytics48:10 - Multidisciplinary Approach in Advanced Cancer Management51:46 - Conclusion and Final Thoughts --- RESOURCES DREAMseq Trial: Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197. doi:10.1200/JCO.22.01763 CheckMate 067 trial: Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025;392(1):11-22. doi:10.1056/NEJMoa2407417

Ep. 543 Metastatic Colorectal Cancer: Discussion on the COLLISION Trial with Dr. Martijn Meijerink

Play Episode Listen Later May 13, 2025 47:58

Is minimally invasive ablation the future of metastatic cancer care? We now have the results of the COLLISION Trial, which investigates the non-inferiority of thermal ablation compared to surgical resection. How will these findings change treatment paradigms and practice patterns around metastatic colorectal cancer? In this week's episode of BackTable, interventional radiologist Dr. Chris Beck discusses the impact and implications of the COLLISION Trial with principal investigator Dr. Martijn Meijerink from Amsterdam UMC.---SYNPOSISThe doctors explore the COLLISION Trial's design, results, complication rates, and future directions. They also cover best practices for ablation techniques and the potential for interventional oncology to enter a “golden era.” Finally, Dr. Meijerink highlights the importance of standardizing intervention quality and being present in tumor boards to ensure optimal patient care.---TIMESTAMPS00:00 - Introduction 03:21 - Understanding Metastatic Colorectal Cancer and IR's Role05:18 - Introduction to the COLLISION Trial07:40 - Radiofrequency vs Microwave Ablation and Technological Advancements09:02 - Trial Design and Patient Eligibility16:20 - Ablation Techniques and Approaches22:05 - Trial Results and Analysis30:19 - Impact on Guidelines and Practice39:44 - Best Practices in Thermal Ablation43:27 - Future Directions in Interventional Oncology---RESOURCES“Surgery versus thermal ablation for small-size colorectal liver metastases (COLLISION): An international, multicenter, phase III randomized controlled trial.” (Meijerink, 2024)https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA3501

impact trial best practices ir guidelines collisions martijn colorectal cancer future directions metastatic radiofrequency amsterdam umc jco chris beck trial design backtable

An Oncologist's Guide to Ensuring Your First Medical Grand Rounds Will Be Your Last: Lessons on How NOT to Induce Coma in Your Audience

Play Episode Listen Later May 13, 2025 27:23

Listen to ASCO's JCO Oncology Practice, Art of Oncology Practice article, "An Oncologist's Guide to Ensuring Your First Medical Grand Rounds Will Be Your Last” by Dr. David Johnson, who is a clinical oncologist at University of Texas Southwestern Medical School. The article is followed by an interview with Johnson and host Dr. Mikkael Sekeres. Through humor and irony, Johnson critiques how overspecialization and poor presentation practices have eroded what was once internal medicine's premier educational forum. Transcript Narrator: An Oncologist's Guide to Ensuring Your First Medical Grand Rounds Will Be Your Last, by David H. Johnson, MD, MACP, FASCO Over the past five decades, I have attended hundreds of medical conferences—some insightful and illuminating, others tedious and forgettable. Among these countless gatherings, Medical Grand Rounds (MGRs) has always held a special place. Originally conceived as a forum for discussing complex clinical cases, emerging research, and best practices in patient care, MGRs served as a unifying platform for clinicians across all specialties, along with medical students, residents, and other health care professionals. Expert speakers—whether esteemed faculty or distinguished guests—would discuss challenging cases, using them as a springboard to explore the latest advances in diagnosis and treatment. During my early years as a medical student, resident, and junior faculty member, Grand Rounds consistently attracted large, engaged audiences. However, as medicine became increasingly subspecialized, attendance began to wane. Lectures grew more technically intricate, often straying from broad clinical relevance. The patient-centered discussions that once brought together diverse medical professionals gradually gave way to hyperspecialized presentations. Subspecialists, once eager to share their insights with the wider medical community, increasingly withdrew to their own specialty-specific conferences, further fragmenting the exchange of knowledge across disciplines. As a former Chair of Internal Medicine and a veteran of numerous MGRs, I observed firsthand how these sessions shifted from dynamic educational exchanges to highly specialized, often impenetrable discussions. One of the most striking trends in recent years has been the decline in presentation quality at MGR—even among local and visiting world-renowned experts. While these speakers are often brilliant clinicians and investigators, they can also be remarkably poor lecturers, delivering some of the most uninspiring talks I have encountered. Their presentations are so consistently lackluster that one might suspect an underlying strategy at play—an unspoken method to ensure that they are never invited back. Having observed this pattern repeatedly, I am convinced that these speakers must be adhering to a set of unwritten rules to avoid future MGR presentations. To assist those unfamiliar with this apparent strategy, I have distilled the key principles that, when followed correctly, all but guarantee that a presenter will not be asked to give another MGR lecture—thus sparing them the burden of preparing one in the future. Drawing on my experience as an oncologist, I illustrate these principles using an oncology-based example although I suspect similar rules apply across other subspecialties. It will be up to my colleagues in cardiology, endocrinology, rheumatology, and beyond to identify and document their own versions—tasks for which I claim no expertise. What follows are the seven “Rules for Presenting a Bad Medical Oncology Medical Grand Rounds.” 1. Microscopic Mayhem: Always begin with an excruciatingly detailed breakdown of the tumor's histology and molecular markers, emphasizing how these have evolved over the years (eg, PAP v prostate-specific antigen)—except, of course, when they have not (eg, estrogen receptor, progesterone receptor, etc). These nuances, while of limited relevance to general internists or most subspecialists (aside from oncologists), are guaranteed to induce eye-glazing boredom and quiet despair among your audience. 2. TNM Torture: Next, cover every nuance of the newest staging system … this is always a real crowd pleaser. For illustrative purposes, show a TNM chart in the smallest possible font. It is particularly helpful if you provide a lengthy review of previous versions of the staging system and painstakingly cover each and every change in the system. Importantly, this activity will allow you to disavow the relevance of all previous literature studies to which you will subsequently refer during the course of your presentation … to wit—“these data are based on the OLD staging system and therefore may not pertain …” This phrase is pure gold—use it often if you can. NB: You will know you have “captured” your audience if you observe audience members “shifting in their seats” … it occurs almost every time … but if you have failed to “move” the audience … by all means, continue reading … there is more! 3. Mechanism of Action Meltdown: Discuss in detail every drug ever used to treat the cancer under discussion; this works best if you also give a detailed description of each drug's mechanism of action (MOA). General internists and subspecialists just LOVE hearing a detailed discussion of the drug's MOA … especially if it is not at all relevant to the objectives of your talk. At this point, if you observe a wave of slack-jawed faces slowly slumping toward their desktops, you will know you are on your way to successfully crushing your audience's collective spirit. Keep going—you are almost there. 4. Dosage Deadlock: One must discuss “dose response” … there is absolutely nothing like a dose response presentation to a group of internists to induce cries of anguish. A wonderful example of how one might weave this into a lecture to generalists or a mixed audience of subspecialists is to discuss details that ONLY an oncologist would care about—such as the need to dose escalate imatinib in GIST patients with exon 9 mutations as compared with those with exon 11 mutations. This is a definite winner! 5. Criteria Catatonia: Do not forget to discuss the newest computed tomography or positron emission tomography criteria for determining response … especially if you plan to discuss an obscure malignancy that even oncologists rarely encounter (eg, esthesioneuroblastoma). Should you plan to discuss a common disease you can ensure ennui only if you will spend extra time discussing RECIST criteria. Now if you do this well, some audience members may begin fashioning their breakfast burritos into projectiles—each one aimed squarely at YOU. Be brave … soldier on! 6. Kaplan-Meier Killer: Make sure to discuss the arcane details of multiple negative phase II and III trials pertaining to the cancer under discussion. It is best to show several inconsequential and hard-to-read Kaplan-Meier plots. To make sure that you do a bad job, divide this portion of your presentation into two sections … one focused on adjuvant treatment; the second part should consist of a long boring soliloquy on the management of metastatic disease. Provide detailed information of little interest even to the most ardent fan of the disease you are discussing. This alone will almost certainly ensure that you will never, ever be asked to give Medicine Grand Rounds again. 7. Lymph Node Lobotomy: For the coup de grâce, be sure to include an exhaustive discussion of the latest surgical techniques, down to the precise number of lymph nodes required for an “adequate dissection.” To be fair, such details can be invaluable in specialized settings like a tumor board, where they send subspecialists into rapturous delight. But in the context of MGR—where the audience spans multiple disciplines—it will almost certainly induce a stultifying torpor. If dullness were an art, this would be its masterpiece—capable of lulling even the most caffeinated minds into a stupor. If you have carefully followed the above set of rules, at this point, some members of the audience should be banging their heads against the nearest hard surface. If you then hear a loud THUD … and you're still standing … you will know you have succeeded in giving the world's worst Medical Grand Rounds! Final Thoughts I hope that these rules shed light on what makes for a truly dreadful oncology MGR presentation—which, by inverse reasoning, might just serve as a blueprint for an excellent one. At its best, an outstanding lecture defies expectations. One of the most memorable MGRs I have attended, for instance, was on prostaglandin function—not a subject typically associated with edge-of-your-seat suspense. Given by a biochemist and physician from another subspecialty, it could have easily devolved into a labyrinth of enzymatic pathways and chemical structures. Instead, the speaker took a different approach: rather than focusing on biochemical minutiae, he illustrated how prostaglandins influence nearly every major physiologic system—modulating inflammation, regulating cardiovascular function, protecting the gut, aiding reproduction, supporting renal function, and even influencing the nervous system—without a single slide depicting the prostaglandin structure. The result? A room full of clinicians—not biochemists—walked away with a far richer understanding of how prostaglandins affect their daily practice. What is even more remarkable is that the talk's clarity did not just inform—it sparked new collaborations that shaped years of NIH-funded research. Now that was an MGR masterpiece. At its core, effective scientific communication boils down to three deceptively simple principles: understanding your audience, focusing on relevance, and making complex information accessible.2 The best MGRs do not drown the audience in details, but rather illuminate why those details matter. A great lecture is not about showing how much you know, but about ensuring your audience leaves knowing something they didn't before. For those who prefer the structured wisdom of a written guide over the ramblings of a curmudgeon, an excellent review of these principles—complete with a handy checklist—is available.2 But fair warning: if you follow these principles, you may find yourself invited back to present another stellar MGRs. Perish the thought! Dr. Mikkael SekeresHello and welcome to JCO's Cancer Stories: The Art of Oncology, which features essays and personal reflections from authors exploring their experience in the oncology field. I'm your host, Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. What a pleasure it is today to be joined by Dr. David Johnson, clinical oncologist at the University of Texas Southwestern Medical School. In this episode, we will be discussing his Art of Oncology Practice article, "An Oncologist's Guide to Ensuring Your First Medical Grand Rounds Will Be Your Last." Our guest's disclosures will be linked in the transcript. David, welcome to our podcast and thanks so much for joining us. Dr. David JohnsonGreat to be here, Mikkael. Thanks for inviting me. Dr. Mikkael SekeresI was wondering if we could start with just- give us a sense about you. Can you tell us about yourself? Where are you from? And walk us through your career. Dr. David JohnsonSure. I grew up in a small rural community in Northwest Georgia about 30 miles south of Chattanooga, Tennessee, in the Appalachian Mountains. I met my wife in kindergarten. Dr. Mikkael SekeresOh my. Dr. David JohnsonThere are laws in Georgia. We didn't get married till the third grade. But we dated in high school and got married after college. And so we've literally been with one another my entire life, our entire lives. Dr. Mikkael SekeresMy word. Dr. David JohnsonI went to medical school in Georgia. I did my training in multiple sites, including my oncology training at Vanderbilt, where I completed my training. I spent the next 30 years there, where I had a wonderful career. Got an opportunity to be a Division Chief and a Deputy Director of, and the founder of, a cancer center there. And in 2010, I was recruited to UT Southwestern as the Chairman of Medicine. Not a position I had particularly aspired to, but I was interested in taking on that challenge, and it proved to be quite a challenge for me. I had to relearn internal medicine, and really all the subspecialties of medicine really became quite challenging to me. So my career has spanned sort of the entire spectrum, I suppose, as a clinical investigator, as an administrator, and now as a near end-of-my-career guy who writes ridiculous articles about grand rounds. Dr. Mikkael SekeresNot ridiculous at all. It was terrific. What was that like, having to retool? And this is a theme you cover a little bit in your essay, also, from something that's super specialized. I mean, you have had this storied career with the focus on lung cancer, and then having to expand not only to all of hematology oncology, but all of medicine. Dr. David JohnsonIt was a challenge, but it was also incredibly fun. My first few days in the chair's office, I met with a number of individuals, but perhaps the most important individuals I met with were the incoming chief residents who were, and are, brilliant men and women. And we made a pact. I promised to teach them as much as I could about oncology if they would teach me as much as they could about internal medicine. And so I spent that first year literally trying to relearn medicine. And I had great teachers. Several of those chiefs are now on the faculty here or elsewhere. And that continued on for the next several years. Every group of chief residents imparted their wisdom to me, and I gave them what little bit I could provide back to them in the oncology world. It was a lot of fun. And I have to say, I don't necessarily recommend everybody go into administration. It's not necessarily the most fun thing in the world to do. But the opportunity to deal one-on-one closely with really brilliant men and women like the chief residents was probably the highlight of my time as Chair of Medicine. Dr. Mikkael SekeresThat sounds incredible. I can imagine, just reflecting over the two decades that I've been in hematology oncology and thinking about the changes in how we diagnose and care for people over that time period, I can only imagine what the changes had been in internal medicine since I was last immersed in that, which would be my residency. Dr. David JohnsonWell, I trained in the 70s in internal medicine, and what transpired in the 70s was kind of ‘monkey see, monkey do'. We didn't really have a lot of understanding of pathophysiology except at the most basic level. Things have changed enormously, as you well know, certainly in the field of oncology and hematology, but in all the other fields as well. And so I came in with what I thought was a pretty good foundation of knowledge, and I realized it was completely worthless, what I had learned as an intern and resident. And when I say I had to relearn medicine, I mean, I had to relearn medicine. It was like being an intern. Actually, it was like being a medical student all over again. Dr. Mikkael SekeresOh, wow. Dr. David JohnsonSo it's quite challenging. Dr. Mikkael SekeresWell, and it's just so interesting. You're so deliberate in your writing and thinking through something like grand rounds. It's not a surprise, David, that you were also deliberate in how you were going to approach relearning medicine. So I wonder if we could pivot to talking about grand rounds, because part of being a Chair of Medicine, of course, is having Department of Medicine grand rounds. And whether those are in a cancer center or a department of medicine, it's an honor to be invited to give a grand rounds talk. How do you think grand rounds have changed over the past few decades? Can you give an example of what grand rounds looked like in the 1990s compared to what they look like now? Dr. David JohnsonWell, I should all go back to the 70s and and talk about grand rounds in the 70s. And I referenced an article in my essay written by Dr. Ingelfinger, who many people remember Dr. Ingelfinger as the Ingelfinger Rule, which the New England Journal used to apply. You couldn't publish in the New England Journal if you had published or publicly presented your data prior to its presentation in the New England Journal. Anyway, Dr. Ingelfinger wrote an article which, as I say, I referenced in my essay, about the graying of grand rounds, when he talked about what grand rounds used to be like. It was a very almost sacred event where patients were presented, and then experts in the field would discuss the case and impart to the audience their wisdom and knowledge garnered over years of caring for patients with that particular problem, might- a disease like AML, or lung cancer, or adrenal insufficiency, and talk about it not just from a pathophysiologic standpoint, but from a clinician standpoint. How do these patients present? What do you do? How do you go about diagnosing and what can you do to take care of those kinds of patients? It was very patient-centric. And often times the patient, him or herself, was presented at the grand rounds. And then experts sitting in the front row would often query the speaker and put him or her under a lot of stress to answer very specific questions about the case or about the disease itself. Over time, that evolved, and some would say devolved, but evolved into more specialized and nuanced presentations, generally without a patient present, or maybe even not even referred to, but very specifically about the molecular biology of disease, which is marvelous and wonderful to talk about, but not necessarily in a grand round setting where you've got cardiologists sitting next to endocrinologists, seated next to nephrologists, seated next to primary care physicians and, you know, an MS1 and an MS2 and et cetera. So it was very evident to me that what I had witnessed in my early years in medicine had really become more and more subspecialized. As a result, grand rounds, which used to be packed and standing room only, became echo chambers. It was like a C-SPAN presentation, you know, where local representative got up and gave a talk and the chambers were completely empty. And so we had to go to do things like force people to attend grand rounds like a Soviet Union-style rally or something, you know. You have to pay them to go. But it was really that observation that got me to thinking about it. And by the way, I love oncology and I'm, I think there's so much exciting progress that's being made that I want the presentations to be exciting to everybody, not just to the oncologist or the hematologist, for example. And what I was witnessing was kind of a formula that, almost like a pancake formula, that everybody followed the same rules. You know, “This disease is the third most common cancer and it presents in this way and that way.” And it was very, very formulaic. It wasn't energizing and exciting as it had been when we were discussing individual patients. So, you know, it just is what it is. I mean, progress is progress and you can't stop it. And I'm not trying to make America great again, you know, by going back to the 70s, but I do think sometimes we overthink what medical grand rounds ought to be as compared to a presentation at ASH or ASCO where you're talking to subspecialists who understand the nuances and you don't have to explain the abbreviations, you know, that type of thing. Dr. Mikkael SekeresSo I wonder, you talk about the echo chamber of the grand rounds nowadays, right? It's not as well attended. It used to be a packed event, and it used to be almost a who's who of, of who's in the department. You'd see some very famous people who would attend every grand rounds and some up-and-comers, and it was a chance for the chief residents to shine as well. How do you think COVID and the use of Zoom has changed the personality and energy of grand rounds? Is it better because, frankly, more people attend—they just attend virtually. Last time I attended, I mean, I attend our Department of Medicine grand rounds weekly, and I'll often see 150, 200 people on the Zoom. Or is it worse because the interaction's limited? Dr. David JohnsonYeah, I don't want to be one of those old curmudgeons that says, you know, the way it used to be is always better. But there's no question that the convenience of Zoom or similar media, virtual events, is remarkable. I do like being able to sit in my office where I am right now and watch a conference across campus that I don't have to walk 30 minutes to get to. I like that, although I need the exercise. But at the same time, I think one of the most important aspects of coming together is lost with virtual meetings, and that's the casual conversation that takes place. I mentioned in my essay an example of the grand rounds that I attended given by someone in a different specialty who was both a physician and a PhD in biochemistry, and he was talking about prostaglandin metabolism. And talk about a yawner of a title; you almost have to prop your eyelids open with toothpicks. But it turned out to be one of the most fascinating, engaging conversations I've ever encountered. And moreover, it completely opened my eyes to an area of research that I had not been exposed to at all. And it became immediately obvious to me that it was relevant to the area of my interest, which was lung cancer. This individual happened to be just studying colon cancer. He's not an oncologist, but he was studying colon cancer. But it was really interesting what he was talking about. And he made it very relevant to every subspecialist and generalist in the audience because he talked about how prostaglandin has made a difference in various aspects of human physiology. The other grand rounds which always sticks in my mind was presented by a long standing program director at my former institution of Vanderbilt. He's passed away many years ago, but he gave a fascinating grand rounds where he presented the case of a homeless person. I can't remember the title of his grand rounds exactly, but I think it was “Care of the Homeless” or something like that. So again, not something that necessarily had people rushing to the audience. What he did is he presented this case as a mysterious case, you know, “what is it?” And he slowly built up the presentation of this individual who repeatedly came to the emergency department for various and sundry complaints. And to make a long story short, he presented a case that turned out to be lead poisoning. Everybody was on the edge of their seat trying to figure out what it was. And he was challenging members of the audience and senior members of the audience, including the Cair, and saying, “What do you think?” And it turned out that the patient became intoxicated not by eating paint chips or drinking lead infused liquids. He was burning car batteries to stay alive and inhaling lead fumes, which itself was fascinating, you know, so it was a fabulous grand rounds. And I mean, everybody learned something about the disease that they might otherwise have ignored, you know, if it'd been a title “Lead Poisoning”, I'm not sure a lot of people would have shown up. Dr. Mikkael Sekeres That story, David, reminds me of Tracy Kidder, who's a master of the nonfiction narrative, will choose a subject and kind of just go into great depth about it, and that subject could be a person. And he wrote a book called Rough Sleepers about Jim O'Connell - and Jim O'Connell was one of my attendings when I did my residency at Mass General - and about his life and what he learned about the homeless. And it's this same kind of engaging, “Wow, I never thought about that.” And it takes you in a different direction. And you know, in your essay, you make a really interesting comment. You reflect that subspecialists, once eager to share their insight with the wider medical community, increasingly withdraw to their own specialty specific conferences, further fragmenting the exchange of knowledge across disciplines. How do you think this affects their ability to gain new insights into their research when they hear from a broader audience and get questions that they usually don't face, as opposed to being sucked into the groupthink of other subspecialists who are similarly isolated? Dr. David Johnson That's one of the reasons I chose to illustrate that prostaglandin presentation, because again, that was not something that I specifically knew much about. And as I said, I went to the grand rounds more out of a sense of obligation than a sense of engagement. Moreover, our Chair at that institution forced us to go, so I was there, not by choice, but I'm so glad I was, because like you say, I got insight into an area that I had not really thought about and that cross pollination and fertilization is really a critical aspect. I think that you can gain at a broad conference like Medical Grand Rounds as opposed to a niche conference where you're talking about APL. You know, everybody's an APL expert, but they never thought about diabetes and how that might impact on their research. So it's not like there's an ‘aha' moment at every Grand Rounds, but I do think that those kinds of broad based audiences can sometimes bring a different perspective that even the speaker, him or herself had not thought of. Dr. Mikkael SekeresI think that's a great place to end and to thank David Johnson, who's a clinical oncologist at the University of Texas Southwestern Medical School and just penned the essay in JCO Art of Oncology Practice entitled "An Oncologist's Guide to Ensuring Your First Medical Grand Rounds Will Be Your Last." Until next time, thank you for listening to JCO's Cancer Stories: The Art of Oncology. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all of ASCO's shows at asco.org/podcasts. David, once again, I want to thank you for joining me today. Dr. David JohnsonThank you very much for having me. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show notes: Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr David Johnson is a clinical oncologist at the University of Texas Southwestern Medical School.

Episode 59. Management of Systemic Mastocytosis with Dr. Daniel DeAngelo

management cancer supplement systemic hematology dana farber cancer institute z39 jco mastocytosis

Play Episode Listen Later May 8, 2025 63:18

In this episode, we discussed the management of systemic mastocytosis with Dr. Daniel DeAngelo from the Dana Farber Cancer Institute. Here are the key studies we discussed:Midostaurin https://www.nejm.org/doi/10.1056/NEJMoa1513098?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.govAvapritinibEXLPORER study: https://www.nature.com/articles/s41591-021-01538-9PATHFINDER study: https://www.nature.com/articles/s41591-021-01539-8Bezuclastinib: APEX trial: https://ashpublications.org/blood/article/144/Supplement%201/659/530240/Apex-Part-1-Updated-Assessment-of-BezuclastinibHSCT for Advanced SM: https://ascopubs.org/doi/10.1200/JCO.2014.55.2018

A look at next-gen oncology

Pharmacy Friends

Play Episode Listen Later Apr 30, 2025 50:54

In this episode, you'll hear about the latest developments in tailoring cancer treatments to individual patients using Precision Oncology. Two thought leaders, Simone Ndujiuba, a Clinical Oncology Pharmacist at Prime Therapeutics, and Karan Cushman, Head of Brand Experience and host of The Precision Medicine Podcast for Trapelo Health, discuss real-world research that is paving the way for Prime and our partners to help providers reduce turnaround times so patients can start treatment as soon as possible. Join your host Maryam Tabatabai as they dig into this evolving topic of precision oncology. www.primetherapeuitics.com ⁠Chapters⁠Defining precision medicine (08:50)Evaluating real-world operational process of biomarker testing (14:36)Turnaround times are crucial (17:40)A patients view into the importance of time (24:39)Technology and process aid in time and process (29:30)Helping bridge knowledge gaps for providers and payers (33:55) The focus is on Precision Oncology right now (37:00)Precision medicine in other disease categories (40:09)Future of precision oncology is bright (42:07) References Singh, B.P., et al. (2019). Molecular profiling (MP) for malignancies: Knowledge gaps and variable practice patterns among United States oncologists (Onc). American Society of Clinical Oncology. https://meetings. asco.org/abstracts-presentations/173392 Evangelist, M.C., et al. (2023). Contemporary biomarker testing rates in both early and advanced NSCLC: Results from the MYLUNG pragmatic study. Journal of Clinical Oncology, 41(Supplement 16). https://doi.org/10.1200/JCO.2023.41.16_suppl.9109. Ossowski, S., et al. (2022). Improving time to molecular testing results in patients with newly diagnosed, metastatic non-small cell lung cancer. Journal of Clinical Oncology, 18(11). https://doi.org/10.1200/OP.22.00260 Naithani N, Atal AT, Tilak TVSVGK, et al. Precision medicine: Uses and challenges. Med J Armed Forces India. 2021 Jul;77(3):258-265. doi: 10.1016/j.mjafi.2021.06.020. Jørgensen JT. Twenty Years with Personalized Medicine: Past, Present, and Future of Individualized Pharmacotherapy. Oncologist. 2019 Jul;24(7):e432-e440. doi: 10.1634/theoncologist.2019-0054. MedlinePlus. What is genetic testing? Retrieved on April 21, 2025 from https://medlineplus.gov/genetics/understanding/testing/genetictesting/. MedlinePlus. What is pharmacogenetic testing? Retrieved on April 21, 2025 from https://medlineplus.gov/lab-tests/pharmacogenetic-tests/#:~:text=Pharmacogenetics%20(also%20called%20pharmacogenomics)%20is,your%20height%20and%20eye%20color. Riely GJ, Wood DE, Aisner DL, et al. National Cancer Comprehensive Network (NCCN) clinical practice guidelines: non-small cell lung cancer, V3.2005. Retrieved April 21, 2025 from https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Benson AB, Venook AP, Adam M, et al. National Cancer Comprehensive Network (NCCN) clinical practice guidelines: colon cancer, V3.2025. Retrieved April 21, 2025 from https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Rosenberg PS, Miranda-Filho A. Cancer Incidence Trends in Successive Social Generations in the US. JAMA Netw Open. 2024 Jun 3;7(6):e2415731. doi: 10.1001/jamanetworkopen.2024.15731. PMID: 38857048; PMCID: PMC11165384. Smeltzer MP, Wynes MW, Lantuejoul S, et al. The International Association for the Study of Lung Cancer Global Survey on Molecular Testing in Lung Cancer. J Thorac Oncol. 2020 Sep;15(9):1434-1448. doi: 10.1016/j.jtho.2020.05.002.The views and opinions expressed by the guest featured on this podcast are their own and do not necessarily reflect the official policy or position of Prime Therapeutics LLC, its hosts, or its affiliates. The guest's appearance on this podcast does not imply an endorsement of their views, products, or services by Prime Therapeutics LLC. All content provided is for informational purposes only and should not be construed as professional advice.

Ep. 538 Immunotherapy and TACE in HCC Treatment with Dr. Julius Chapiro and Dr. Richard Finn

planning trial decision treatments studies ucla final thoughts yale university organizing variations immunotherapy future prospects hcc piis0140 practical insights tace jco chris beck ch3

Play Episode Listen Later Apr 29, 2025 67:37

There are now multiple phase 3 studies on combination transarterial chemoembolization (TACE) and immunotherapy showing a significant benefit over TACE alone. How do these findings change the hepatocellular carcinoma (HCC) treatment algorithm? In this multidisciplinary episode of the BackTable Podcast, Dr. Richard Finn (Medical Oncologist at UCLA) and Dr. Julius Chapiro (Interventional Radiologist at Yale University) join host Dr. Chris Beck to discuss immunotherapy, TACE, emerging trends in HCC treatment, and the future of the field.---This podcast is supported by an educational grant from Guerbet.---SYNPOSISThe doctors highlight the importance of high quality clinical data and the pivotal studies shaping current best practices. They explore the role of the different players on the multidisciplinary team and compare the oncologic and radiologic perspectives. Additionally, they discuss the synergy between TACE and immunotherapy, the criteria for selecting appropriate treatments, and the ongoing need for research and collaboration.---TIMESTAMPS00:00 - Introduction 03:35 - HCC from an Oncologic Perspective 05:33 - Radiological Perspective on Liver Cancer06:50 - Referral Patterns and Organizing a Multidisciplinary Approach18:01 - Explaining TACE and Variations in the Procedure27:27 - Choosing the Right Procedure for HCC36:13 - Making a Decision on Medical Treatment Candidacy 42:23 - Importance of Data Driven HCC Treatment, Practical Insights, and Studies to Know55:30 - Planning an Approach for a TACE Procedure01:02:26 - Final Thoughts and Future Prospects in Liver Cancer Treatment---RESOURCESBarcelona Staging System:https://www.ncbi.nlm.nih.gov/books/NBK569796/table/Ch3-t0001/TRACE Trial:https://pubs.rsna.org/doi/full/10.1148/radiol.211806PREMIERE Trial:https://www.gastrojournal.org/article/S0016-5085(16)34971-X/fulltextEMERALD-1 Trial:https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.LBA432LEAP O12 Study:https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02575-3/abstract

BRCA Reversion Mutations

Play Episode Listen Later Apr 24, 2025 12:43

BRCA revision mutations may explain some of the limited benefit seen in long-term follow-up studies with PARP inhibitors. Bibliography: 1: BRCA reversion mutations predict resistance. https://doi.org/10.1158/2159-8290.CD-18-0715 2: SOLO3 Final OS Data. https://doi.org/10.1200/JCO.24.00933 3: Elucidating acquired PARP inhibitor resistance in advanced prostate cancer. https://doi.org/10.1016/j.ccell.2024.10.015

cd mutation brca bibliography reversion parp jco elucidating

Ep. 522 Advancements in Treatment of Metastatic Ocular Melanoma with Dr. Altan Ahmed and Dr. Sid Padia