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The Accelerators Podcast
Oncology News and Views from Photon Media. For more info, please visit photonmedia.org.
The Accelerators Podcast
Intro to Radiopharmaceutical Therapy (RPT) with Ana, Brandon, and Dustin
Accelerator Dr. Matt Spraker hosts Drs. Ana Kiess, Brandon Mancini, and Dustin Boothe to review radiopharmaceutical therapies (RPTs), aka theranostics.
The first episode in this TAP miniseries starts by reviewing how we define radiopharmaceutical therapy for our patients and colleagues. We review Lutathera and Pluvicto including indications for treatment.
We then review aspects of training and how we've collaborated with nuclear medicine and radiology in training and practice.
We close the episode scratching the surface of RPT radiobiology, beta versus alpha emitters and BED concepts.
The Accelerators Podcast is a Photon Media production. For more from Matt, visit his website. For more from Simul, visit his blog, Radiation Medicine: Dollars and Sense.
Welcome back to the accelerators. So I've got that slide. Thanks for being here. Let's get on with it. Welcome back to the Accelerators Podcast. This is going to be really exciting to me. We have a great kind of series of episodes. So it's going to be one of a couple where we talk about a very hot topic in radiation oncology, which is radio pharmaceutical therapies. And the idea for this show actually came from we recorded a patient episode about this on the other podcast, Oncology Up Scripted. And I think that has some good information as well. But the goal of these episodes is to really provide a nice medical education background for this topic for our field physician staff, everyone that's treating with these therapies. And so I am Matt Spraker. I'm a radiation oncologist in Denver, Colorado. And we'll go ahead and have our guests introduce themselves.
SPEAKER_00:Thanks, Matt. I'm Anna Keese. I'm a radiation oncologist at Johns Hopkins, and I specialize in radiopharmaceuticals and external vein radiation for prostate cancer.
SPEAKER_04:Hi everyone, I'm Brandon Mancini in Grand Rapids, Michigan, and I'm medical director at Banff Health, where I've completely transitioned my career to all radiopharmaceutical therapies, standard of care, and clinical trials.
unknown:Right.
SPEAKER_03:I'm I'm Dustin Booth. I'm a radiation ecologist out in Utah. I help uh lead the system for intermount help for their radiopharmaceutical efforts on the clinical and the research side. Uh and then I'm also the director of uh a free standing center called Utah Cancer Specialist and happy to be on.
SPEAKER_01:Let's just start out. Um, remember, a lot of our audience is trainees, and we kind of gloss over this a lot, but maybe someone could just give a definition of what a radio pharmaceutical is and like how do you explain to patients what that is? If they come to you with the term therapnostic, do you correct them? Um can you give us a little bit of back like kind of your thoughts on those terms and how we should be talking about these therapies with patients?
SPEAKER_03:Yeah, I can I can do it. So um, you know, this is something that I really didn't understand until I got into the field in more depth. Um, but but really radiopharmaceuticals can consist of both the diagnostic and the therapeutic side. Um, you know, a radio pharmaceutical FDG, for example, is a radio pharmaceutical for FDG pets. Um, and uh same with PSMA pet, right? Those are those are radiopharmaceuticals on the diagnostic side. And then there's the the the therapy side. So the therapeutic side, and we've been using these for for decades, right? From iodine, um, uh and uh you know we've had evolution into things like radium-223 and um we had the XR and Zevel in the radioimmunotherapy days. Um so there's the therapeutic, radio pharmaceutical, and there's the the diagnostic, and in the theronostics is this particular um relationship between those two where the diagnostic um radiopharmaceutical um shows it has the same target as the therapeutic. And so we use these, um we've been using that paradigm you know in iodine for for decades, um, right? And we use the iodine scan, and then we also deliver a therapeutic that has the same target for these thyroid cancers. And so um the theragnostics is this unique um a relationship between that diagnostic and the therapeutic. Uh, and uh it's becoming more as you know, hence this this whole um podcast is becoming more popular. There's lots of uh new and evolving treatments that have this diagnostic and a therapeutic pair where it's the same target, and we can use them to predict response and eligibility for therapies in a really unique way that's never been looked at um to the extent that it's being looked at now.
SPEAKER_01:I like that answer a lot. I think I I we I asked actually Ravi Patel the same thing on the patient podcast because I I like that uh this idea, especially sharing with patients, that it's this idea that you scan them, identify the target, and then you're giving a therapy that goes to that target. It makes it it's very it's also very radonk like, right, to kind of have that have that happening.
SPEAKER_04:We like to say you see what you treat, you treat what you see. So it's kind of a super unique aspect of medicine where there may not be any outside of Theranostics where you literally can see the target, you can evaluate what your therapy's doing uh in real time outside of kind of traditional blood-based biomarkers or or others.
SPEAKER_01:So yeah, and I do have patients too that I know in the past have been like they like they're sort of hesitant about chemotherapy, but they're much more open to what we call targeted therapies, right? Because the idea that you're able to hone something that goes all around the body, but just specifically to where it needs. So I think emphasizing that point to the patient about these therapies is going to be helpful along those lines as well.
SPEAKER_00:The language is often very confusing, especially for trainees or people who are new to the field, because there's a lot of overlapping terminology and different institutions or organizations have different preferred terms. So, like in astro and and radiation oncology, a lot of times we're referring to radiopharmaceutical therapy. That's our committee name, that's like our name of our round table. And um, you know, that is coming uh on my end from George Skoros, who's the medical physicist who has led a lot of the development and disymmetry in this field, um, and from like many of the physics committees. You know, Novardis prefers radiolygent therapy, SNMMI and EANM have different preferred terms. There's targeted radionuclide therapy, peptide receptive radiotherapy usually refers to ludothero, but it can refer to other peptide-based treatments. Some people refer to prefer targeted molecular radiotherapy, and then theragnostics kind of pairs with the imaging, but not all therapeutic agents have paired imaging agents. So it's very confusing, but it essentially usually is synonymous. So it's just um kind of helping people to understand that these are all referring to the same general field.
SPEAKER_01:Yeah, and I'm not suggesting that we kick off another like naming debate in the field. We have plenty of those. Do you, but I guess just to close the topic, do the three of you have a term that you use when you walk around your offices and you talk about this? What do you what do you call it?
SPEAKER_00:I changed it up. I sometimes say theronostics, I sometimes say radiopharmaceutical therapy, sometimes radio lichen, sometimes radio nuclear. I switch it around.
SPEAKER_04:Yeah, I would agree. And uh a lot of times for patients, I might just call it a radiation medicine, just to kind of get it into like it is therapy or it is something that's doing something to help them. Um, but yeah, same here as far as the synonyms with uh theronostics or molecular targeted radiation therapy or radiopharmaceutical therapy.
SPEAKER_03:Yeah, and we're not you, you know, we're uh not a stranger to that, you know, external beam therapy versus VMAP versus it, you know, we have a lot of terms for different things. Uh no, for sure. Yeah, something you said, Matt, that that I really I really love, and partially why I think this field is so fascinating is that you know we're able to see and predict response based on these images in a unique way that you can't with any other test, you know. Uh you can do a PDL1 test, or you can do um you can do a genomic test, and you can look and see what sensitivity somebody has based on a blood or tissue test, but you can't really see that mapped out for an entire patient's tumor birth, right? Uh but we can we can create a target that we can image and you can look at 10, 20 tumors, and you can see how there's heterogeneity and uptake, and and um, and that results in heterogeneity of response. And so you can really predict response in a really unique way. Whereas if you just give somebody immunotherapy, you don't know that half of those tumors may be susceptible uh where the other half won't. Uh and so it's it's it's a really cool way to to really bring up those images with patients and say, hey, you're you're a good candidate. I mean, look at all of your tumors, look how avid they are. Or you can say, you know, uh, there's some that aren't so avid. We're gonna watch these closely closely and see how they do. And we have other uh tools at our disposal potentially to help down the line.
SPEAKER_01:Oh, that's really interesting, actually. You um let's save that because I actually have a question about this coming up, but I've never I have not thought about that yet. And I think that's a really cool aspect of dosimetry and I guess imaging query that that could help guide therapy in the future. So that's really cool. So it's it's good for listeners to know you mentioned already, Dustin, that like this has been around for a while. This is not a new concept, but I think that it's new in a lot of people's mind because it's becoming more popular. And I was hoping in these episodes to focus on the popular therapies right now. And so uh the two that we'll kind of talk about mostly are gonna be Pluvicto and then Lutothera. Um, and I was wondering if maybe someone would be willing to kind of talk about what these actually are. Um, and then maybe their indications as well, just so we can kind of set the stage for further discussion of these therapies.
SPEAKER_04:I can do uh Lutothera and maybe Anna could do uh prostate cancer. So yeah, so Lutothera, so uh Lutothera itself is um Lutetium-177 uh based, which is kind of both pluvicto and lutothera in and of itself. But that's the FDA-approved uh Theronostic treatment or radiopharmaceutical treatment for uh neuroendocrine tumors. And so interestingly enough, it's been around and FDA approved since January of 2018, um, and really didn't make as much of a splash as we've heard over the last couple of years with pluvicto and prostate cancer, um, largely in part because of kind of just the incidence and prevalence of most neuroendocrine tumors, right? Um there's uh about uh 8 to 16,000 new cases of neuroendocrine tumor diagnosed every year in the United States, where there's about 300,000 new cases of prostate cancer. And so that in and of itself uh is kind of uh potentially uh a major factor there. Now with Lutothera, so it's a somatostatin receptor or somatostatin analog-based therapy, and it's an infusion-based therapy. Um, it's given once every eight weeks for four times, and it's for classically gastroenteropancreatic neurondocrine tumors or GEP nets, uh, with the kind of expanded ability to deliver it in pulmonary neuroendocrine tumors and some other somatostatin receptor-positive tumors. Um, but uh infusional therapy typically given over a period of multiple minutes. Uh you have amino acids that are delivered with that to protect the kidneys. Um, and it's typically indicated uh for patients with grade one to three tumors. Classically was approved for patients uh with tumors that had previously progressed on somatostatin analog monotherapy, where more recently, over the last couple of years, uh the indication has been to actually consider to move it in the upfront setting or the initial management of grade two and three neurondicum tumors, um, when their KI 67% is 10% or greater, um, and so forth. Um, even more so, uh the indication is actually expanded down to age 12-year-old children uh for gas uh for neuron tumors. So that's kind of unique uh in and of itself. Um kind of covering kind of a wide variety not only of neurondicumers, but also uh kind of bridging the gap of of uh pediatrics in adults and and so forth as well. Um again, kind of as I alluded to, it's once every eight weeks for four times. The PET scan that's typically associated with it is an dota-tate or dota talk-based PET CT. So, again, based on what we've been talking about, you're identifying the target, ensuring that you have adequate expression of said target, and then that patient qualifies for treatment.
SPEAKER_01:That's a great explanation. I actually had know about the pediatric, or I guess, well, technically in the US pediatric indication, or I guess we can call it AYA, but that's also really cool. And is it so is that the only radiopharmaceutical therapy that's eligible for patients under 18?
SPEAKER_04:Yeah, there's some in clinical trials for things like neuroblastoma and others and other earlier phase trials for sarcoma as well that allow down to age 16. Um, but really, yeah, 12 and up uh with uh lutathere is the only uh radiopharmaceutical for kids.
SPEAKER_01:That's really cool. Um, how about pluvicto, Ana?
SPEAKER_00:So pluvicto or lutetium PSMA617 is FDA approved uh since 2022 for men with metastetic castro-resistant prostate cancer. And it was initially approved based on the vision trial for patients who had already had prior taxane chemotherapy and androgen receptor pathway inhibitors like aberrantone or enzymatamide. And more recently, there was an FDA approval added in 2025. Uh the expansion the indications were added for patients who had not yet had taxane-based chemotherapy but were uh candidates for delaying taxane chemotherapy. So still after androgen receptor pathway inhibitors. So I think there is also some debate going on about the potential addition of an indication in the future based on the PSMA addition trial, even earlier. But as of right now, uh most centers are following the currently FDA approved indications based on PSMA 4 and the vision trial for patients who have had prior receptor pathway inhibitors. And of course, they also have to have a positive PSMA TET scan based on the vision criteria. So um there are lab criteria as well. Um there's different um criteria that people use. There's an SNMMI consensus paper that is quite nice about sort of updated lab criteria that are appropriate for newly screened, uh newly uh consulting patients.
SPEAKER_01:I'm gonna save that topic for later because I think it's a fascinating one. But I did see that paper came out, or like that study was kind of reported this year that kind of tried to move Pluvicto up to first-line metastatic treatment for patients with prostate cancer. And it's sort of at least, I mean, again, I'm a generalist here, not a specialist in the subfield, and I kind of just see this stuff online, but it sort of seemed like it landed with a little bit of a like not a ton of enthusiasm from people that do this, where they were kind of like, well, they I know that the end point was a little controversial, and it doesn't seem like, at least in my practice, that we are super excited about delivering it that early. But I was I I'm definitely gonna ask you guys about that later because I think it's an important topic for sure. And so I wanted to shift gears a little bit and talk about um how how we're training for this, because I think that this is something that, you know, as a general radiation oncologist, you're probably hearing about it more and more. And then we might even start to see some like administrators coming up to people and asking if we want to kind of start a program. Um and it's something that I think uh it sounds like a lot of the experts agree needs to be more available out in the community. And so um my training experience with this was I think a lot of people, I graduated was similar to a lot of people's. I graduated in 2018 from residency. I trained in Seattle, and how at that time it was basically like a criteria that we had to meet to be able to qualify to graduate. You have to go to a certain number of cases, and it where I trained, it was it was done by nuclear medicine, and there was always a little bit of like contentiousness about training radiation on colleges to to do this procedure. But I did get it done. I got those done, and then I like went on to my first job and had some kind of in-house training about their workflows, and then I was kind of blessed to be able to do it. And when I moved to my new job in Colorado, they actually the state accepted my prior cases as like training evidence. And and so I'm now like I'm on the license and I can kind of do it in our practice again with internal training about the workflows, but um certainly like I do not feel as experienced as the you know at radio pharmaceuticals compared to like, for example, um, you know, guyne breaky therapy, which I do all the time and did a ton in training. And so, so I was curious to hear all of your thoughts about discussion of training where it is right now, if there are challenges, and then what kind of trainees now can expect to see in 2025 as they're graduating in terms of boards and things like that. I'm assuming this will become more tested since it's kind of becoming a front-of-mind topic for the field.
SPEAKER_00:Thanks, Matt, for sharing your own experience. I think a lot of um practicing radiation oncologists in this area have a similar story as you. And um obviously with a new disruptive technology um and um multiple disciplines, multiple disciplines involved, I think the training and education needs are really high. And um we'll need to go through iterations because you know, we would love for everyone to have like a hundred cases and months of dedicated experience in their training programs and many, many criteria for competency that are very well accepted and established. And there are international groups like the IAEA that are working to establish such criteria, but right now that's not feasible in the United States, and like if we required that no program would meet their ACGME requirements, they'd all be um under review, and the candidates wouldn't be able to um serve their patients. So essentially, I think it needs to be an iterative process, and we've been doing some iterations of changes. So um our committee through Astro and the ACGME and the ABR are all very aware of the need for increased training, and the number of required cases has increased most recently to eight cases. Um and there's a proposal that's under review right now at the ACGME to increase the minimum to 13 cases with 10 pereneral and at least two different agents, which is similar to what the current nuclear medicine requirements are in the United States, and also to specify the hot lab experience more clearly and the faculty um engagement. And I think that that is likely to be our sort of new goal soon, um, but not for long because we're gonna need to increase that even more the next time that that's feasible. And um and you know, how we actually um implement that at each institution and training program is gonna be very specific to that institution and who does what at that institution. And um, you know, I think that as much as possible, we need to collaborate with nuclear medicine to make sure that as many, as many young and junior people are trained uh to do this as possible.
SPEAKER_01:I was actually gonna jump in and be like, you know, I wonder if we really need as many cases as, for example, um a complex long, you know, like long SBRT, right? Where there is a lot of technical component to making sure that you do it safely. And I guess in my head, I was thinking, well, this is just giving a drug, right? But I think at the end of the day, there actually is some technical expertise required on the QA side, like you said, with the hot lab and understanding what the physics team is doing. And so that's a really good point, and and probably a justification for increasing exposure to these cases for trainees in general. I don't know if you guys have things to add, Dustin or Brandon. Go ahead, Dustin.
SPEAKER_03:Oh, yeah. Sure. Um, I'll just to um point out uh what you said about the the complexity of it and how it relates to other things we do. Um you in certain settings it can be very simplistic. Sometimes you're you have a really well trained staff. You got a you know you're in a big hospital or a big academic center and you've got a half a dozen nuclear medicine technologists who inject patients all day with radio pharmaceuticals. And and for them you know now that that particularly plebicto is in a 20cc syringe, the complexity has gone down over time for that standard care and delivery of plubicto in particular. But we do have some settings where um there is no nuclear medicine technologists because they're in short supply. And you may have a freestanding clinic or a smaller hospital that relies on the radiation team to deliver these therapies and to deliver them well. And so knowing how to work with your staff, your physics team and your nurses and your whole team to deliver these, I think it's really important for people to understand, to get that education for our residents to know. And just because you know now that Pluvicto's in a 20cc syringe um we don't know what the future is like and the complexity of these. And so we want to train um our our residents and our colleagues to do these confidently and do them well in any setting. Because you don't know when you're training what job you're going to have and what you're gonna be asked to do. And the better exposure you get, the better prepared you're gonna be to lead your team to give really good quality care.
SPEAKER_04:Yeah and I think the the heterogeneity of uh kind of where programs are at throughout the country, whether it's academic or non-academic is still kind of in flux or evolving. So I think that's super important as well where yeah I mean it's still trying to figure out is this going to be a NukeMed thing, a radon thing or a combination thing? That is still evolving as institutions are kind of coming along and figuring out how to navigate that space. And just to touch on the training even beyond, either even like radiation therapists and nuclear medicine technologists, the evolution of a potential hybrid uh training or more advanced training within that space is likely uh to happen just based on conversations and some of the things evolving in their own training programs as well. And so I think you'll see NukeMed Radon continue to become even more intertwined, work together and also training not only your authorized users but those that can assist with delivering these therapies safely at high scale.
SPEAKER_01:That's I'm gonna actually take your segue that you gave me there because I did want to ask you guys about collaboration because I think that's a really important topic. So I'll just like repeat again when I trained I got my training in NewMed like that's where we went the department to get the training they were very nice to train us and kind of sign off on our cases. And then nowadays what in our practice our um I work in a multi-hospital network in Denver in our practice uh we deliver at one site but it's actually uh logistically done by the radiation oncology physicians and clinical team so like nurses but then we use the nuclear medicine technicians to actually like help schedule and receive and deliver it. And it's a great collaboration. In fact the techs are like rock stars and it makes it so easy for our department so it's it's awesome. And so that's I think that's maybe a little bit of a unique setup but there is variability. So could you three share your experiences collaborating with nuclear medicine folks just at your institutions if applicable and kind of how that's been for you.
SPEAKER_03:Sure I'm happy to so um so kind of uh um uh the way that our program well we've been delivering greedy pharmaceuticals at Intermount Health uh for a long time um and it's gone through different evolutions but really where this came uh to be um a big issue to work through is when Plubic Doe uh was FDA approved and we had this huge demand and we had this huge health system to meet this demand. Uh and then um uh some people wanted radiation oncology to do it at our main center other people wanted nuclear medicine um at that point radiation oncology had been delivering Zofigo um and nuclear medicine had been doing uh lutithera um and there wasn't really much you know much qualm about it it's just how how it panned out at the time but this was kind of the it was this bigger deal that came on you know a lot of administrations you know came through and so um ultimately it started with radiation oncology and I I led that program um but I you know some some feelings were hurt to be honest um and it didn't roll out great um and um but but we just forged forward and uh as I got really busy I needed a partner and um I had some of my colleagues were pretty lukewarm about what I was doing to be honest. Some of them really didn't see any value in it. I cared about it. I I saw the potential um and so I had the kind of the opportunity like oh I could bring a colleague from another hospital to come help me my colleagues locally aren't really interested like but I've got this nuclear medicine uh doctor who's awesome and smart and interested and I was like why don't we re-engage um and and see if he'd like to to do this with me. And I I also saw where the field was going. I wanted to I wanted to build phase one through three trials. I I wanted to do dosymmetry I wanted to do spec all this stuff that was really going to take a lot of collaboration between me and nuclear medicine department. And so I thought you know I think I think that it could be really valuable to have somebody with skin in the game in the program um and to build something that that that would be unique. And so um my colleague Eric Hughes just a fantastic doctor um a really great guy and um you know we worked some things out and we decided to to do it together and split it up in a certain way. And so we we we rolled out that essentially we had this kind of hub and spoke model and uh and then started rolling it out to other hospitals. It was more challenging finding nuclear medicine physicians or radiologists available to have this dyad model. We wanted to have a dyad model but it it hasn't panned out perfectly sometimes it works sometimes it doesn't I mean there's always a radiation oncologist that's it that's willing. And so most of our programs at our peripheral sites are smaller hospitals or other regions are anchored with radiation oncology but we have this strong central core where we have a tumor board where you know nuclear medicine radiation oncology work really well and we do have some hospitals that that preserve that dyad model. But uh and then at the at the free standing center is just radiation oncology but we have nuclear medicine technologies we have a PET CT there. But but I want to say like the things we're capable to do um in a community setting really um escalated when we made that partnership. We really were able to do some great things together that I think if I would have just um stepped into the nuclear medicine department said, all right, I'm in charge, we're doing this, we're doing that, I'm not sure it would have panned out as well as it has. You know all the things we've been able to accomplish on the you know dosymmetry and spec CT and our phase one through three imaging and therapeutic trial program it really I I owe to the the great collaboration we have. And so I I value it and I think it's really important when it's available. It's not always available and there's always not always interest right and and that's and that's important to know you don't always have to have a model as as intertwined as ours is but I do think that there's some great benefits and it has been really beneficial for our system. It hasn't been easy I won't say it's perfect, right? Whenever you collaborate with others there's differences in opinions and sometimes things take longer than they otherwise would and you know sometimes you give up things that you want to do because of somebody else and you know um but I think as a whole I'm I've I've been happy with how it's been fit our system Anna how about you so I got into this field by working in the laboratory of Martin Clomber who was my research mentor for my residency research year which was a postdoc year for me here at Hopkins and you know he really inspired me to want to do this for the rest of my career.
SPEAKER_00:And he was the inventor of DCFPYL which is Tylerify the F-18 PSMA pet imaging agent that is most widely used in the United States. So he's been a radiochemist for decades and basically is like the godfather of PSMA. So we did some of the first translational experiments in animals and um alpha energy emitters targeting PSMA and doing microtosymmetry and mapping on like tumor response and um normal organ toxicity. So that was a very exciting segue into joining this field. At Hopkins uh similar to what Dustin was saying radiation oncology was doing Zofigo and Nuclear Medicine was doing Ludithera. And then when pluvicto came uh to be FTA approved in 2022 what we ended up doing was sort of a side by side model where um nuclear medicine does the pluvic those at the main campus here in Baltimore and Radiation Oncology does the pluvic dose at Green Spring Station, which is our outpatient center in the county and at the Sibley Memorial Hospital in DC because we already had established clinics with physicians and nurses and staffing at those locations. And at those locations we administer independent of nuclear medicine using um a combination of clinical clinical technologists nursing and physics staffing along with the physician like resident and attending. So we would love to have a nuclear medicine technologist also engaged at those sites and you know I think we have room for a lot of improvement in terms of like having a truly combined program instead of side by side and having like combined tumor board which we don't have things like that. So I would say side by side is okay. We reach a lot of patients we are safe and we have high quality care. We have a lot of trials open but we could um be more efficient I think both economically and in our research startup times and in our like uh effort for staff and faculty if we aligned more.
SPEAKER_04:Yeah and I think for us I mean kind of the unicorn center in the United States in the sense that it's a vertically integrated dedicated freestanding theronostic center that's unaffiliated right so it kind of was that ability to foresee the landscape and how things are changing and our CEO kind of with his history in as a radiochemist and and so forth and physicist behind the scenes kind of seeing what was coming down the line and then having the ability to to launch a center such as this. Obviously myself as a radiation oncologist we're super passionate about like finding people that want to do this and do this at a high level. And our senior medical advisor came from Germany and he was a nuclear medicine physician doing theronostics with 10,000 rounds of experience over 13 years. I went over to Germany for some time and spent time there. We took a lot from Germany and Australia with Peter Mack and Michael Hoffman and Louise Emmett and everybody as far as kind of initiating the program. So kind of just taking and trying to utilize best practices but with the luxury of just being a center that is de novo brand new came and cropped up out of nowhere and kind of establishing things in the way that we think is best to serve patients and to assist with clinical trials at advancing the field and et cetera. But anytime we're looking for expansion for authorized users, new team members, et cetera, I mean it's the right skill set from both of those walks of life that are super important and even beyond when it's all said and done. So obviously as radiation oncologists, we have that vast uh training in oncologic management. So we're very uh kind of uh used to uh the oncologic discussions and the kind of the in-depth aspects of treatment management and patient management, nuclear medicine with the superiority and the imaging side of things. And then I think very realistically in the future you're going to see either the budding of a fellowship-based uh subspecialty or eventually its own subspecialty depending kind of on the number of of new agents and kind of the timeline for which those develop. And so I think as the field grows, you just really need passionate people that want to do it from both and definitely at institutions kind of collaborating as they see fit. And that's going to continue to evolve as time evolves as well as you get champions within the space from both specialties.
SPEAKER_01:So I really appreciate all you sharing those stories because I think that this is it's nice to hear that like it's not all roses every time right like there might be some bumps in the road things like that. And then something that you all said you're all in different settings right so we have like academic, non-academic big hospital network and then the freestanding kind of dedicated center. And I think what comes through from all three stories is that you want to find a passionate collaborator to help build the program and it kind of doesn't really matter what their background is as long as they're passionate. And just for the like kind of the audience, if you're if they're sitting out there in a center where there's no program and they're looking for collaborators, basically this can be done by radiation ecologists, nuclear medicine physicians, also radiologists, right? I think I had a I know somebody that built their program with IR. So those are kind of the people that can that can do this right and so that that might be who people could approach to start the conversation if they're looking for a physician collaborator. Is that right? Are there other doctors that I forgot about or are those kind of the three fields that have expertise that could be put on as a as an authorized user and run a program?
SPEAKER_04:Oh yeah it's really that authorized user background that's important Ana. Yeah.
SPEAKER_00:It's also really important though to also consider like medical oncologists and urologists as um key partners both not just as referring physicians but in like the ongoing management of the patient longitudinally and in sort of considering how you want to set up your program to meet the needs of the patients that they are sharing with you.
SPEAKER_03:So you see variability in pullback Go being used in different settings even when you have available authorized users. And I think that's really interesting because when you think of multidisciplinary care you also have to recognize where those referrals are coming from and that is you know predominantly your medical oncologist and your and and now a urologist. And so you have different preferences from those referring doctors of when to use this modality and this drug. And sometimes I I do worry um that we want to come in strong and capable and passionate, but we don't want to take it over from our referring doctors. We want to engage them, keep them engaged, find out what's important to them in managing their patients. Some docs want to be involved and want to see those patients in between every cycle. Some of them just like hey set it forget it you're you're good go. Others want to be a little you know more engaged and so I I think it's really important no matter where you're practicing when you think of multidisciplinary care that you don't forget where your referrals are coming from and and really making sure that um they they they know the benefits of it and the ability and the cap and the potential but that we don't say um come in too strong and say hey this is my thing not yours. You know this is a systemic therapy and our referring um doctors that's that's what they do day in day out and they have a great expertise and some of them want to be really involved in care. And sometimes if you you push them away or you don't engage them you may cut off a referral pipeline or or or or result in not using it as much. So just just thought I'd share that.
SPEAKER_01:No that's a that's a great point. And I and I think the reality is for a lot of us like there we're generalists, right? And so you a a team is always great because you you're not just doing this and so like you're you know you're you're doing a radiopharmaceutical case between your SBRT and brachiotherapy everything else you do. And so it helps to have support especially we'll talk next episode about like kind of the toxicities but they are unique compared to what we're used to dealing with. And so I think that that's a that's really an awesome point. I appreciate you bringing it up thank you. I wanted to to change topics again and ask a little bit about how you all feel like this fits with external beam radiation therapy. So kind of two aspects to this question. First one is say you're a generalist at a small center and you have a busy practice with external beam radiation therapy but you do feel this is important so you're passionate about getting this started. For for those of you, sorry Brendan, for those of you that are doing external beam and radio pharmaceuticals, do you feel like this has impacted your like volumes or practice or can you speak a little bit about fitting this into the other things that you're doing throughout the day? The second question is going to be about combining these therapies with external beam and that'll be more of a research based question.
SPEAKER_03:But let's start with the first part just logistically sure you know Anna Anna you're a little more on the research side so maybe I'll I'll I'll just talk about the practical aspect of how it's affected my practice. And uh and just uh just yesterday I saw a consult for a patient um who uh was cast newly cast rate resistant had moderate volume disease at the time of presentation um and had been on uh ADT and um and an ARPI for uh almost two years and um had PSA had been tracking up and did a scan uh the medical college did a scan and saw that there was uh that there was avidity uh which I've we've talked about uh you know between two of us and so they knew it was a good candidate so send s send the patient to me um and there's only two spots uh and um there was you know only two areas of avid disease uh only two areas of of that that assume is the causing the progression and we walked through it and um you know I'm gonna give that patient SBRT to those two sites uh and then we'll keep plebicto in our back pocket uh for uh if and you know when they when they do progress. And so I I've had a number of uh cases like that. Um and it's been really cool to be involved um and to treat those patients, follow them, uh see the good response um and then uh and then and then also see them and for plebicto you know when they they progress. So that's one setting that I've I've seen um you know over and over and uh and do so. The other is of course palliative uh you know for palliative uh and prophylactic reasons um a couple months ago I had a patient that had that came in to see me and had a moderate volume disease but a lot of disease in their femur in their femoral neck and uh that that patient was obviously at risk of of of fracture um and so we ended up doing radiation uh to the to the um to the femoral neck and and head there uh prior to treatment um and then also there's the use of it during so sometimes these patients uh again a patient yesterday that uh progressed uh PSA is progressing on treatment and they're progressing uh in their spine and and uh causing symptoms and so I'm gonna treat them with palliative radiation before you know before I send them back. And of course I'm communicating with the medical oncologist like hey you know we're gonna I'll do this and and let's talk about the next line of therapy. But there's there's a lot of exciting uh I think avenues beyond that in terms of catering and and uh um looking at partial response and consolidated and things like that. Maybe Anna can speak more to that. But just in my practice, I I certainly have seen it in the use of my external beam side of my brain more so than I think patients are are really receiving if they're getting chemo right and never seeing a radiation oncologist. And I I I think that that's a better care for the patient, honestly. So it's it's it's great to be involved and I've seen that in my experience.
SPEAKER_00:I would agree with everything Dustin said. Almost every patient that I treat with Lubicto or Zof, I also treat with external beam radiation of some kind. And you know as these drugs move into earlier line earlier stage treatment, the evolution of what kind of external beam is appropriate in that setting will also be changing. So like when pluvicto was first approved and it was only after taxane chemotherapy and it's usually last line therapy. Typically I would be treating patients like as I'm meeting them in consultation and starting to set up like the order and having to wait a few weeks to start pleubicto giving a short course of one or five conventional fractionated 3D CRT to the painful sites. Or at the end if they're progressing and they're coming off of pluvicto that I would potentially be treating them at that time. As we're moving earlier and now we're pre-chemo, there's a lot more patients that have smaller volume disease are more appropriate for metastasis directed SPRT. We may be more aggressive in treating those sites in combination or treating sites of oligoprogression like if you're having a patient who is generally responding well to pluvicto but has just a few sites that are progressing with um either clinically or on imaging may be appropriate for metastasis directed therapy in that setting. And then on the research side at Hopkins we've had um sort of a specialization in treatment of oligometastatic hormone sensitive prostate cancer and this started with food trans work with the Oreo and the Raven studies. So Raven was uh SPRT plus or minus radium 223 and that did not show benefit. I think um published presented that at Astro 2024 and we believe that's because it's really not effectively targeting micromedacitic disease because it only works in areas with bone turnover. It's not molecularly targeted. There's a similar study ongoing that we have open at Hopkins the Novartis phase three D study which is the um SPRT plus or minus Pluvicto for umligomedacitic hormone sensitive disease. And we heard the presentation of the lunar study at Astra this year that was not with Pluvicto but with lutation PSMA lantheus um formulation that is um not no longer being produced unfortunately so um that um study though did show a really significant improvement in progression through survival with the with the lutation PSMA therapy even with just two cycles. So we are really hopeful that um with the molecular targeting that that will be positive the D study with Novartis. And then we also have a study we're about to open for divinitive therapy in combination with external being and six months of hormone therapy for hybrid localized prostate cancer. So it's external being conventional fractionation or moderately hypofractionated with pluvicto and six months of ADT so that's something we're really excited about and moving even earlier. So different types of combinations and we have physicists like Rob Hobbs and George Soros who are really experts in combined dosymmetry and we've had studies with RAI and way before with samarium doing combined dosimetry. So we're utilizing that to really delve into the um to the combined bioeffective dose.
SPEAKER_01:Especially with prostate like with our historic kind of problem where we have a local therapy and we kind of all believe there's micrometastatic disease in higher risk patients like it almost seems like a scientific inevitability that we're gonna we're gonna see combined therapies like down the road because we just you know it's it's been a problem we've been aware of for so long.
SPEAKER_04:Brandon do you have anything to add to kind of what's been said so far about combining uh uh radiopharmaceuticals with external beams no I think a lot of the consults I see kind of are the same way where maybe a medical oncologist or urologist sends that patient over for evaluation because they meet the metastatic castration resistant prostate cancer space. They've had their ARPI, they've been on ADT, but then the radiation oncologist takes a look at that PSMA pet and sure enough it's three or absolutely five or less type of metastases and they're sending them for systemic therapy with pluvicto but then I kind of redirect them to radiation oncologists with the capabilities to do SBRT. So that just happened today in a consultation that happens many times a month where it just emphasizes the importance of radiation oncologists being involved in this process, whether it's a multidisciplinary theronostics tumor board or as that authorized user that is playing a major role within Pluvicto and other theronostics treatments because again we have that knowledge and appreciation for that aspect of the data and how it fits in with everything. So I think that came up in both instances with the the ongoing and future studies as well as kind of the daily experience for Dustin too.
SPEAKER_01:When you do studies at your center like are you able to collaborate and do these combined studies with like with another radiation collegist that treats the external beam part? Is that kind of how you'll be doing this going forward for your setup specifically?
SPEAKER_04:Yeah and it depends study by study. I mean whether it's principal investigator, whether it's co-PIs, sub eyes, et cetera but yeah you can actually successfully designate an institution to carry out certain aspects of the trial uh with the oversight uh and so case by case basis, but yeah it allows us to to collaborate which if anything it's actually uh really great because then we're collaborating with uh the hospital systems in town so that we can make sure that they their patients have access to all these unique trials.
SPEAKER_01:Oh that's awesome. Okay so we're getting towards the end here of our time for this episode. I wanted to just kind of close out with one question about radiobiology actually I this is the first time I was telling you guys before like when uh before we recorded here that like this is the first time I've actually used chat GPT to kind of like push back on me and see if that should add anything to my outline for the show. And it and it actually spit out does the linear quadratic like kind of mental model apply for radiopharmaceuticals? And I was like oh shit I I actually don't know. And so and I think it's a really good question but let's let's like make it a little bit more general. So and let me start with Anna with this one just with your expertise here. So like when we're thinking about the radiobiology of these drugs right in my head I have like radiobiology of breaky radiobiology of external beam those are kind of different the way we train them and then like how is it for this? I mean should we be thinking about the same the same I know we're not prescribing Senegray specifically but how should radiation oncologists think about radiobiology in a unique way for radiopharmaceuticals compared to how we're trained with external beams great question.
SPEAKER_00:So essentially um it's different for betas and alphas so beta emitters like lutetium 177 or iodine 131 basically emit electrons and radiobiologically have a lot of similar similar properties to treatment with x-rays or photons. So RBE is similar um and the linear quadratic equation applies and there still is a difference though in the biologically effective dose because radiopharmaceuticals are um given at a much lower dose rate really much lower um compared to um external beam radiotherapy and so there's sort of an ongoing DNA damage and repair that needs to be accounted for in a biologically effective dose. So the equations are different for BED for uh lutetium 177 versus photon treatment and also obviously it's not fractionated the same way um that we do for uh daily conventional radiotherapy alpha emitters are a linear or log linear uh relationship they so there's uh much more double strand DNA breaks and um that quadratic component where you have like accumulated subletal damage that is not there for alphas so alphas have a different radiobiology than betas and much different than exterior photon therapy and they also have a much shorter range um the RBE uh is really to be determined for many alphas in development um it could be anywhere from like five to twenty um and it's uh very um the BED the typical BED equations are not as applicable either for alphas so that is sort of a very quick summary.
SPEAKER_01:That's great I appreciate it I think that's I think the goal here is to get people thinking about it. These are gonna they're obviously open questions and I think you could probably do a whole episode just on just on the topic. Anything to add Justin or Brandon for thinking about this with your with your treatments?
SPEAKER_04:No I mean I think everything's spot on and also just that slow release over the time we a lot of times we call it gentle radiation. It's also depositing that radiation from the inside out for something like Pluvicto with the majority of it being deposited over a fraction of a millimeter. So it's like slow release very gently over time to a very confined area as opposed to your external beam, which is still highly accurate, right? Where your dose clouds are going to be within millimeters of uh your target uh and and so forth. Um but just that inside outside approach and just that kind of slow release over time it's it's a it's a very nice way of of hurting the cancer and keeping things nice and conformal and keeping normal tissue toxicity down.
SPEAKER_01:All right well I want to thank you all very much this is uh episode one of our series the the goal here was just to cover some of the interesting like high level topics around this I think it's fascinating and I appreciate your insights and so uh we will um kind of see you back for for the next one in the in the future so I really appreciate that thank you all very much if we liked ourselves