Oncologic intervention

Episode Transcript

Good afternoon everyone. This is Dr. Michael Soulen. I’m the Director of Interventional Oncology at the Abramson Cancer Center and Director of Interventional Radiology Research at the University of Pennsylvania. I’m here with Dr. Dan Brown and Dr. Bulent Arslan, and we are live at SIR in a soundproof booth, located at the Cook booth. Today we’re going to have a conversation about interventional oncology, and we’re going to start with some introductions. So I’m going to have each of my co-podcasters say who they are, where they’re from, and tell us– from starting as an interventional radiologist–how did you become an interventional oncologist? So, over to you, Dan.

Thanks, Mike. I’m Dan Brown. I’m Vice Chair of Innovation and Clinical Research at Vanderbilt, as well as Director of Interventional Oncology. I started practice in 1999 and I was at Mallinckrodt Institute, and you basically built a niche there or you put on in a lot of central lines and tubes, which was okay, but if you wanted to build a practice, you had to find something. And no one was really doing interventional oncology there at that point, and the transplant people found me as a junior faculty. I started working with them, and then the randomized trials for case hit and life got really busy really fast and it was awesome. It was a–it was a great experience. My primary mentors included Will Chapman, who is the director of liver transplant at Vanderbilt. He taught me how to think more in a cancer way, just in regular research. And I was also fortunate enough to work with Mike Darcy and Dan Picus. And I’ll pass it over to Bulent.

Awesome. So my interventional oncology adventure started kind of almost a little late in my career. My mentor–initial person who trained me–is David Waldman from Rochester. That’s where I did my residency and fellowship. He’s an awesome, hardworking guy. And then I did like three years at a VA, which I did kind of PAD mostly, and that’s what I liked. Then I went to University of Virginia, over to Dr. Mike Dake and Alan Matsumoto and Fritz Angle. I learned a lot from all of them. But then, you know, after my second year, I knew I was going to go to Moffitt Cancer Center and I started doing oncology at that time just to prepare myself; I hadn’t done much until then. But when I arrived at Moffitt, they did no cancer intervention almost at all. It was–the only thing that was done was, you know, intraoperative ablations and some bland embolization for neuroendocrine.

So I worked on getting a Y-90 program. We started that. We were number one in TheraSphere radioembolization (??) on the second year. There was so much potential in the place. We quadrupled the volume every year in–two years in a row. And that’s when I started loving more and more what I do in oncology. And then when I transitioned to Rush, we did the same thing at Rush. We bumped pressures oncology volume almost four times from what it was. And that’s why I still love it and I’m happy to be involved with it.

I had a similar experience, you know, starting out. I mean, I was fortunate that in my training I was exposed to interventional oncology, both as a resident at Hopkins and a fellow at Jefferson. But, you know, the little bit that existed was run by the oncologists, not by the interventional radiologists. We were kind of the plumbers; you know, they wrote the orders, they admitted the patients. And then, you know, I did a research fellowship, but it was all in biliary disease, not in cancer. And then I came to Penn on faculty, and of course, Constantin Cope was there. So I was not going to become the bile duct person when Dr. Cope was already there. So, like Dan said, you have to find a niche. And you know, no one was doing any oncology there, and at least I’d been exposed to it.

And the funny story was that one day the phone rang and I picked–it was an indie angiographer (??) called–I pick it up and it’s a guy, a patient, self referring for TACE. He had a metastatic neuroendocrine tumor and he knew he needed to be TACEd. And he had been relocated by his company to Philadelphia, so he just called Penn. So I thought this was cool. I said, well, I know how to do that. So I, you know, dutifully called the very famous head of GI Medical Oncology and said, “Wow, I’ve got–it’s been self-referred, this guy, and he’s a fascinating guy. He’s got a glucagonoma. Would you see him and admit him so I could embolize him?” And his response was, “What am I, some kind of hospital whore?” Llike, “Why would I admit a patient that you’re treating?” So I’m like, okay, well I know how to do this. So I saw the patient in the office–we didn’t even have a clinic back then–and admitted him and treated him. And we were off to the races. And frankly, you know, I had a great relationship with this oncologist, but he was very clear that he expected us to take care of our own patients. And so that was actually the whole impetus for starting the clinical practice, was so we could do interventional oncology. And like Bulent said, it just–once you start, it just grows and grows and grows.

Yeah, I think especially the referring docs, once they send the patient to you–the more seamless you make it for them–ordering follow-up scans, setting up the clinic, ordering the labs and stuff you need, and taking care of all that stuff–then they look at it as an advantage. It’s less work for them, and you just want to make it as seamless as possible, and that really helps the models grow, right?

Yeah. I mean, I hope we’re past this stage, but when I started at Moffitt, just like you said, all the orders–the oncology clinics were placing the patients on my schedule. We had no control whatsoever. TACE–they would admit, they would put it on, and I wouldn’t know what I’m doing the next day. So I said, “This can’t be–like, they need to kind of consult us,” etc. And my chair said, “Well, if you go that route, you’re going to upset your referers.” I said, “No, I won’t. They’ll like it. They’ll have a full patient care, they won’t have to deal with the coags, the details, et cetera.” So for about six months I saw patients in my office, and after that bothered everyone else in the department they found me an office space and we started a consulting system. And that also helped, like, to grow exponentially faster. Everyone likes that, all referers

Yeah, once they get used to it. You do have to teach them. I mean, in the beginning it can a little bit of an issue. There are some places where IR still can’t get admitting privileges or can’t write chemo orders, but I think for the most part, you know, we’ve shifted over. And I still get new oncologists that come into the system from somewhere else where they’re not used to having an IR service, and it takes a little while to adjust to the fact, but, you know, we make it very clear that you cannot order an IR procedure, you can only order a consult, you know. And then–but once they see that you’ll see the patient and take care of everything seamlessly, and then they just get them back at follow-up time–like you said, they’re very, very happy.

Yeah. It’s–you know, when I got to Vanderbilt in 2013, the transplant guys were used to managing all that stuff with the HECs when I got there. And then I remember I called one of them because a patient called us back and I said, “Hey, just to let you know, patient X called and had a couple questions.” And he’s like, “You took a call from a patient?” He was not upset, but he was just surprised. And then within a couple weeks we’d set up a whole thing where we would take all phone calls in the first two weeks because that was going to be treatment-related, and everything else was probably cirrhosis-related and then they would get back involved. But this, again, is just how to help offload their work and do the things that are related to what we do.

So let’s move on to our next topic of conversation and that is, sort of the trends in practice, in terms of liver-directed therapy, particularly regarding, you know, chemo-mobilization, which was sort of the classical benchmark from the eighties on, to more and more use of Ytttrium-90 radioembolization, particularly in patients with HSC, but also for metastatic disease. So I’ll kick it to Dan first. What’s your view of the relative roles of TACE versus TARE in both primary hepatic LI disease and also in metastatic disease? Do you see that as an evolution, or how’s that going?

I think, you know, for segmental disease we’ve definitely transitioned to Y-90 or, you know, ablation as well. But Y-90 and radiation segmentectomy, I mean, patients generally need fewer treatments of that one tumor. And if they’re on the transplant list, you can bridge them, often successfully. But chemoembolization is a good treatment; it’s been around a long time. In the AASLD guidelines coming out, BCLCB patients, patients with intermediate HCC, the first recommendation is chemoembolization still. You know, there is some Y-90 data there, but you know, chemoembolization still plays a role in HCC. For neuroendocrine, specifically, we do a lot less Y-90 than we used to. I actually like using conventional TACE in them even though the tumors may not be chemosensitive because the bland embolization recoveries are tough. It’S hard on the patient. It’s not a bad treatment, but it’s hard on the patient

I agree completely. I mean we transitioned from TACE to Y-90 in the majority of the cases just because Y-90, we use it more selectively. And then if the tumor is really too large, you know, TACE is a little bit too harsh on the patients. The lobar goes to Y-90 selective, you can do ablation with Y-90 right now, the dosimetry changed so that’s part of the reason. In the older way of doing it, you know, TACE, Y-90, maybe wasn’t so much different. And the Y-90 is obviously a lot more expensive, so you use TACE in those cases. But now with the dosimetry changes, we get ablation with Y-90 just like we do with the regular needle ablation, so that steers us more towards Y-90 lately. But if a patient is going to be bridged to transplant and I know he’s going to get a transplant in the next couple months, then you need tumor control, then spending that extra money doesn’t make sense, then TACE makes more sense in those patients. That’s how it preps.

And Bulent, how about the more–the different scenario of the metastatic patients, let’s say colorectal or nets where you may have, you know, 20 lesions scattered through the liver, not so easy to do assymetry on those. So how do you handle those patients?

That those are obviously very frustrating right now You can, how much Y-90 somebody a couple times, et cetera. I have actually done cases that I use Y-90 and then I switched to yttrium based drug-eluting beads and then try to use selective when things come up, you know, combined with ablation. They’re very complex and every patient you have to kind of gauge it on its own and try to come up with a plan.

Yeah, I think we have a similar experience in that. I mean some of it’s institution dependent. So for example, in our transplant program, the bridging procedure is TACE. I mean that’s just been my policy forever. Not that they’re not so open to doing ablation or Y-90, but it’s just been the default forever. And as you said, you know, if someone’s listed they’re going to get a liver, you know, you don’t need to kill yourself to bridge that person. You know, probably TACE as good enough. But if you think they’re going to be on that waitlist a long time and you have an ablative therapy, that may be better. I think for the non-transplant patients though, you know, the ability to do more potently targeted therapy with Y-90, where you can do good patient-specific dosimetry and not–you know, for those patients, because you can segment out the tumor. You know, that’s evolving. And I think, you know, Dan raised the point about the data–you know, one of the limitations is, there is ancient historical but positive controlled data for TACE in HCC. You know, all the initial trials for Y-90 were negative. The latest systematic analysis basically concluded that there was zero evidence of survival benefit from Y-90 in HCC, but that was all with first generation docimetry. And now that we’ve learned how to do it better, you know, those studies are all going to have to be redone. And then I think, you know, part of the problem with the guidelines that Dan alluded to is, you know, they’re not going to change until you have the evidence. So even though we all know we can do this, we’re going to have to update those studies. The metastatic patients are much more challenging because I think, you know, if you–I mean my practice is mostly neuroendocrine tumors. If you sit down and try to segment 50 metastases–like, no one’s going to do that, right? So it’s very, very difficult. And so I think we still tend to do more non Y-90 based therapies on our metastatic patients. Although colorectal–you know, we have the EPOCH study now showing benefit in second line, for colorectal. I think we all are very convinced about the benefit of–in the salvage setting–of Y-90. It’s very well tolerated by the patients. But like you said, Bulent, you know, if I want to do TACE, I’ve now switched to DEBIRI, you know. So I also do DEBIRI for my colorectal patients as opposed to conventional TACE for my nets and HCC patients. Because again, there’s an area where we have evidence. There’s trials–you know, prospective trials–several of them now, with DEBIRI in colorectal cancer that are from Europe that are very intriguing and promising. So that’s been my bet.

Yeah. One other point: the evolution of docimetry–starting with docisphere especially–we need to do that for other tumors, right? We need to do it for colorectal and you know, potentially neuroendocrine too, to find out where the target dose is. And even cholangio–I mean if MISPHEC hits, I think that would be great. MISPHEC being the trial in Y-90 plus chemo for cholangio carcinoma, for our listeners. You know, as we go, we’re going to need to figure that out for all these different tumors to make sure that we’re dosing at the optimum levels, like we learned we weren’t doing necessarily with HCC.

Yeah, I mean it’s interesting that way before those dosisphere study–the way that I do segmental Y-90 is we dose the whole lobe and deliver segmentally. That’s how we have been doing. So our average dose has been like between 500 to a thousand gray on every–for the past–when did we start? In 2009? Since then. And we have had dramatically better results. So I was kind of–I didn’t know the docimetric differences at the beginning, that people were calculating per segment volume for 200 specifically. So I was frustrated for a while why the results are not reflecting what we are seeing. And then when that sphere study came out, then everyone is on the same page right now pretty much.

I agree. I think the–we’re going to see really, really solid advances in segmental and sub lobar therapy with Y-90 because we can. I think the challenge is the metastatic populations and how we’re going to do dosing. And most importantly, when they have, you know, diffuse enough disease that you would want to treat the whole liver to get all the tumor and now you’re exposing the entire liver and running particular risk of late liver toxicities. You know, how are you going to mitigate that? You know, what is the safe liver dose as opposed to the goal tumor dose? You know, it really shifts from the efficacy to the safety question when you have diffuse disease like that. And I think one of the things that I have not heard a consensus on is what’s the threshold for the safe liver dose? You know, is it 80, is it 60? Is it 40? And you know, is it different from the cirrhotic versus the heavily chemotherapy-treated colorectal patient versus the net patient with a totally normal liver.

Right. And then with partition modeling specifically, what’s the tumor to normal ratio? So how much of what am I putting in is going to go to the tumor and how much is going to go to normal liver? Meaning that the mapping study may be a diagnostic study for therapy, a therapy selection. You may say that the tumor to normal ratio is low enough here that anything that’s even holistically good enough is not appropriate, so we we’re going to do TACE here instead.

Yeah.

So one other thing that–I don’t know if you guys have the tool that– made a huge impact on our Y-90 practice is a CT-fluoro hybrid room. I know there’s cone beam CT, but CT-fluoro hybrid room has made another step difference for us. For the colorectal cases that I have a few, we use the same technique. I just find out where the lesion is–it’s a small, you know, like 60, 80 cc cubic area–and then I blast it with Y-90, at least a 500, 600 grade, if not more. And then we’re getting ablated results. It’s not a lot–I’m hoping to publish it at one point–but we have about 10, 15 patients that we completely ablated those metastatic lesions with Y-90 when they’re oligometastatic instead of diffusing.

All right, let’s pivot to talking about clinical trials. We’ve all been involved in clinical trial research, so let’s chat a little bit about, like, what are the trials that are going on we think are going to–either have impacted practice or are going to impact practice. So I’ll go to you first, Dan.

So one of the trials I’m waiting to see and so I’m hoping Michael will talk about it in a minute, is RETNET. You know, I’ve been personally involved with the resident registry for the last decade and it’s really started putting out papers in the last two years. And one of the reasons that I pitched that trial initially was that, you know, Riyad and a group at Northwestern had done a fantastic job of publishing on glass microspheres, and there was just a dearth of literature in the resin space, and we were using them and so I said, “Let’s do this. And then we can also identify maybe benefits in orphan type tumor patients.” The colorectal patients were published last year in Radiology and we found that the overall survivals were similar with the treatments. And the HCC survivals are similar as well if you go by BCLC glass–between glass and resin. I’m not talking about segment activities, I’m just talking all BCLCAs, all BCLCBs, and Riyad has mentioned that as well at the podium, which has been great. So I think one of the things I say a lot of, “If you get familiar with the tool and can use it well, you can have good results with it.”

I mean, I will have to say, I know that there’s positive results in the SIRFLOX as well as the EPOCH, et cetera, but I wish the results were more convincing so that we wouldn’t have to explain it to the oncologists and other people, you know, why it still helps, et cetera. So I would have to say that the results didn’t–at least those studies–impact my practice too much. I think we may have to design things maybe a little better. Radiation oncologists thought that–, “Great.” They never come up with a study that doesn’t–that’s equivalent or negative. Somehow they know how to get the positive result. We need to kind of do more trials, obviously, get more patients in, and then, like, show the benefit that we know it happens. We need to just show it in a trial fashion, more convincingly. The one trial though–correct me if I’m wrong, if you’re aware of it–the COLLISION trial that’s in Europe. It’s, like, being terminated early because of the significant benefit on the ablation side as opposed to surgery. So that may impact our practices hugely because now surgeons get all those patients way before we do. Now it may change with the results of that trial.

Yeah, you mentioned the radiologist oncologist and it raises an excellent point. You know, they are excellent. I mean, when they want to look at a new application for, say, SBRT of HCC, you know, three big institutions who have protons all get together. They bang out an 80 patient single arm prospective phase two study that’s, you know, not randomized, but it’s still level one evidence and it gets into the guidelines. And, you know, every now and then I get beat up in a tumor board because I don’t have any data, but you know, the radiation oncologists have a cooperative group for the last 40 years. So they have a mechanism where they can just get together and fire off one of these studies. And we don’t. Like, you know, if we had a cooperative group for interventional oncology, you could get a bunch of people together and do a prospective multi-center ablation study, you know, whether we’re talking about thermal ablation or ablative radiotherapy, you know, Y-90 or whatever it is, and run off our own multi-center single arm studies and then we’d have as good evidence as they do, but we’re handicapped by lack of that kind of infrastructure.

Yeah, and going back to resin, I mean, that was a prospective observational study, which is not randomized control, so it doesn’t have the same level of evidence.

Yeah.

But one of the things that I was hoping to do with that is identify sites that if we could create an interventional oncology cooperative group–and I think there are a number of sites from that that could participate, including in community hospitals, which is where a lot of IR is practiced, right? And I think one of the things I’d like to discuss in the next couple minutes might be, what are some future IO studies that you would like to see performed to help supplement the field?

Yeah, I think that we have–you mentioned RETNET, which is for those who are not familiar with it is, randomized embolization trial for neuroendocrine tumors–and we basically took patients with progressive neuroendocrine tumors that were well differentiated, and they were randomized initially to bland embolization, conventional chemoemobilization, and drug-eluting embolic strategies. You know, trying to answer the age-old question of bland versus TACE. And the out–you know, that study was run at 14 centers around the world and it completed accrual approximately a year ago, April of ’22. So the endpoint is hepatic progression, so we’re just waiting for progression events to read out. So I’m hoping that sometime this year, you know, we’ll have had enough events occur that the statistician will pull the trigger and run the analysis. So hopefully we’ll have an answer.

And that trial has, you know, three outcomes really. So the primary endpoint is going to be PFS, but we also looked at adverse events and toxicities, and we also did patient-related quality of life. You know, so even if after 40 years of doing bland and TACE, it turns out they are pretty similar in terms of ecologic outcomes, you know, maybe there’ll be differences in toxicities. Dan already alluded to how much more painful bland embolization is than conventional chemoembolization and that might affect quality of life scores. So I think the outcome of that, we’re going to learn a lot. One of the things that we already learned is that drug-eluting bead embolics as a platform is way too toxic in neuroendocrine tumors that had been suggested in two prior phase two studies, both of which closed because of the high toxicity rate.

And now in a randomized trial it was also demonstrated that it’s just way too toxic with a 40% SAE rate. So that DEB arm was actually closed at the first safety review by the DSMB and is now in the, you know, already migrated to the NCCN guidelines saying you should not do DEB-TACE in NETs. So in fact, we’ve already influenced practice and the study hasn’t even read out yet. I think, you know, obviously trial-based evidence is essential for us. And I love Dan’s comment about having a trials group. You know, I doubt the NCCI is going to give us millions of dollars to do that, but that doesn’t mean we can’t do it. I mean, the fact that we could do the RETNET study, the fact that Dan could do the resin registry, you know, with large numbers of sites precipitating–participating–in standardized data entry, it shows that we can. And even if we don’t have an official structure, we have the skill and the will and the sites and the ability and the people to do stuff like this.

It’s just that each individual trial or study we do has to be individually funded and structured because we don’t have a homebase to do everything. But maybe as the volume of this goes up and up and up, you know, that will happen organically. Also, the Society of Interventional Oncology now has, in addition to its preclinical grant program, has a clinical trial structure, so they’ve started the ACCLAIM trial to–your allusion to COLLISION–you know, called the colorectal ablation study–that’s international, Europe and US, multiple sites trying to approve the efficacy of microwave ablation in colorectal metastases. So now we have a society-run clinical trial that’s multicenter, which again is a model for potential future trials. But you know, we don’t have an infinite resources or infinite structure to grow these things. In terms of the future trials, my personal belief is that our future lies in combining what we do with systemic therapies.

You know, it’s not going to be standalone anymore. And that’s everything we do, whether it’s any of the ablation technologies, whether it’s TACE, whether it’s TARE, but combining them with different types of systemic therapy. So most of my own studies that I’m running now at Penn are some sort of combination trial. I’m very excited about immunoembolization in renal cell carcinoma. You know, renal cell carcinoma, we’ve known since Sid Wallace’s studies in the eighties as one of the few tumors where if you embolize the primary, there’s a predictable abscopal response. You know, they had responses in 10 to 15% of patients, and you know, they had no drugs back then in the eighties. Also if you embolize the primary recell (??) carcinoma, even if the patient goes on to a nephrectomy, their survival doubles across all stages, versus if you never embolize that tumor.

So pretty solid evidence that we do something when we embolize these patients. Now what if you combine them with checkpoint therapy? So now we have phase one trials where patients get started on standard of care, first line, dual checkpoint therapy, and after the first two doses we embolize the primary and then they continue the checkpoint therapy. And, you know, you see what happens to the metastatic lesions. Our first patient in that study had a hundred metastases, lungs, pancreas, lymph nodes. They almost all went away after this combination. Now that could have been the drugs, that could have been the embolization, could have been luck, but, you know, so that’s why we need the whole series. But I mean, it just absolutely blew me away. And you’ll be seeing that report in JVIR very soon.

Yes. That’s amazing. I’m glad I am in this podcast. I’m learning a lot in the process.

So I think, you know–and there’s probably, what, a dozen studies out now looking at combinations of immune checkpoint therapy with various forms, mostly in HCC, right? But with either TACE or TARE, or even with ablation. So that’s a huge area of investigation right now.

Yeah, we had several actually, abscopal effect on children cancer interventions. We have a fibrolamellar program, as well as our osteosarcoma group, sends patients for peripheral lesions, diffuse metastatic, you know, stage four. So the one patient, the whole right lung is full of tumors, and then the other lung started having a tumor. We tried to control the ablation, we used pulse electron field ablation treatment. The whole left side comp had actively (??) went away, the tumor started shrinking on the contralateral side.

Amazing.

We’re all amazed. And it’s like–even the oncologist is amazed. Now she’s–every patient she gets, she wants me to ablate them right now. It’s crazy. I don’t know what it is. There’s a lot unknown, but there’s some truth to that, how it happens.

Which goes to show that we need to up our science. Like we all know this can happen, but we want to know why it happens and how do you make it happen. So when you start doing these as official trials, like you need to do the–you know, the blood sampling, the tissue sampling, learn the immunobiology, what’s happening in these patients. And if we understood why this happened, then we could probably figure out how to make it happen.

I think another part of that–and I agree with everything you’re saying–is also incorporating more research training into the IR residency. I think–because if we want to have people doing the, let’s just crank out an 80 patient study, you know, get level one evidence, we need better study structure. I think a lot of studies have been structured in a way which makes sense at the time, but then when you go to look at the data, it doesn’t work out so well and we really need to do that. And I agree with all the combination therapy ideas. I think we’re still working out what goes first sometimes between checkpoint inhibitors and local regional or vice versa.

Yeah.

What’s the gap? Which drugs, which treatments? Another thing that I think we need to investigate, going back to Bulent’s point about colorectal cancer and hesitancy among medical oncologists is doing a salvage trial perspective. That could be with drug or it could be by itself. Because in the patients that are resistant to other things that have liver dominant disease, the bar would not be so high.

Correct.

And I think there’s a much better opportunity there for a positive trial that would help get that into guidelines and out of footnotes.

Yeah, that’d be great. Because it is–sadly it is almost all retrospective. I think Nick Fidelman at UCSF did a TAS-102 Lonsurf Y-90 trial in salvage for colorectal. So, you know, there’s definitely opportunities to do this with regorafenib or Lonsurf or some of the other standard salvage drugs. But again, prospective data, way more impactful than not.

Mm-hmm.

You know, I love your comment about the research training. I mean, I think, you know, almost all other specialties incorporate research training into the residencies and we have yet to do that. But now that we have a residency, you could think about that. And the other thing we need to do is we need to grow our clinical trial as subset within IR. And you know, for that, fortunately the RSNA has an amazing clinical trials methodology workshop.

It’s a six day boot camp. I’ve been faculty on that for over 10 years. And you know, when I first started teaching there, I succeeded Gary Dorfman, who’d been teaching before me as the sole IR faculty member. And there was like one IR student, all the rest were diagnostic radiologists, so it was my mission to bring IRs to that program. And we’ve now trained, you know, between 30 and 40 over the last several years who’ve gone through that program. And if you look at the yield, it’s terrific. I mean, actually in terms of like doing trials, getting grants, getting published, the IRs do even better than the DRs. So, you know, that’s an opportunity for at least–for young faculty, if you want to get involved in clinical research, you know, take the RSNA course. And Jim Spies is the other faculty member for that course.

So he and I are working together on trying to create an IR version of that course that we would probably do jointly with SIR and SIO to make it a little bit more focused on really the issues facing us and not so much the diagnostic radiologists, but again, provide a pathway for people to learn how to do clinical trials. Because you know, once you understand the language and the logistics and the statistics and all that regulatory stuff, you know, it makes it much easier for you to actually get involved in what’s a very really difficult project.

And I think the other thing is making sure for people that want to do that kind of work, that they can land in jobs where they can do that. Because during RESiN, one of the things I know is a couple of sites had to close because they lost their research support in their department. So you know, the sites that have that kind of support and can do those things, but–and the NCCN type cancer centers and the NCI cancer center should all have that stuff available to them. That’s a great opportunity for people that work there to do the course, because that is a great course. I know people that have gone through it. We’re sending one of our diagnostic people there this year who’s very excited about going. And I encourage anyone out there interested in doing more research in this to pursue that course.

Yeah. I think the other challenge you alluded to is exactly what you said. You know, you can’t do it without the infrastructure. You know, whether it’s your department’s infrastructure or your cancer center’s infrastructure. You know, some places are incredibly well set up like, you know, Mallinckrodt, Wash U, you know. Rich Walls, the chairman there, and he basically has a clinical research core there. They hired like 15 people to support trials and every division can just use those people and you don’t have to, you know–and that’s amazing. Whereas like a place like Penn, we’re all a little fiefdom. So like Nuke Med has their research core and Neuro has their research core and IR has our research core. I mean, it’s very inefficient and costly to do it that way. And of course, but if you don’t have those resources, you can’t do trials. You know, it’s–you can’t even be a site for a trial unless you have that kind of structural support. So, you know, finding ways to help build that around the country would be great. Probably it’s just teaching people what they need to have so they know it–know how to do this properly

And it all comes down from the road. I’m going to ask something that’s kind of probably out of the context. What do you guys–it’s kind of linked–what do you guys think that, if IR should have a integrated residency track that includes a PhD with additional research here? Would that be something that would make sense or feasible?

A master’s degree perhaps, would be something like that. I mean, it could include statistics.

Yeah.

Because a lot of institutions don’t have dedicated statisticians, and that can be a hangup, that can be a real problem if you’re not trained in it. But I think there’s a lot of opportunities, especially at institutions that have advanced imaging cores like, like Mallinckrodt and also like Vanderbilt where we have a whole building. It looks like an Apple store, it’s gorgeous with all kinds of advanced imaging like PET and MR you can learn–do tracers to check, you know, results live, and stuff like that. I think getting advanced training and different things would help just advance the research further and get us in the new avenues we haven’t explored yet.

Yeah, I think a PhD would be very aspirational. Certainly there are MD PhD programs during medical school. but Dan’s absolutely right. I mean, we have quite a number of residents in the Penn program who get master’s. You know, it’s sort of baked into their, you know, we have all these different tracks. You can get a master’s in translational research, you can get master’s in clinical research, you can get master’s in healthcare quality, you know, so–You have to be at a university that supports those kind of things, but I think you’re absolutely right. You know, baking that in as part of the research training experience of a IR residency, I think, you know, at institutions that offer it, is a great idea and quite a number of our–even IR–residents have done that along the way at some point.

Yes. I mean, linked to that, the next step is, I guess now that we are a residency, it opens up a lot of opportunities. What do you think about fellowship training in IO within IR residency after you finish? I know every institution gives a lot of training in interventional radiology that includes oncology, but a dedicated year? Would that help?

I think that’s where we’re going. And Bill Rilling very eloquently went through this in the Dotter lecture. I think all service lines of IR are expanding, right? Including, like, GU, you’ve got prostate embolization, you know, we’re doing more fibroid embolizations than ever before. There’s all kinds of service lines that can develop. I think IO is the first and most logical one to develop. But I think inevitably there’s going to be a number of potential fellowships out there for people that have specific interests. IO is set up. It’s also ideal to have a research integration of training, if it’s like a one year fellowship, something like that, to help make better researchers come out. Because oncology research is as rigorous as any other part of medicine, for sure, and I think that’s inevitably going to happen down the road.

Yeah, I agree. I mean, Bill did a great job in his talk looking at, you know, really what are the sort of ACGME and regulatory definitions of, like, what justifies having a fellowship. You know, like a distinct body of knowledge and skills and experience that you can not get from a residency alone. I mean, so, you know, clearly there are some codification around what elements you would have to have to justify a fellowship, which I think was super important. I wasn’t aware of all those. I totally agree that that’s where we’re headed. I mean, it just makes sense that once we have a residency, we’re going to have oncology fellowships, venolymphatic fellowships, arterial disease fellowships. I mean, you know, there’s a level of sophistication, all those things that, you know, no one resident is going to get. I think the, you know, part of the pushback we get–you know, of course we batted this around our own institution is, “Well who are these fellows going to be?”

I mean, they’re going to be like a seventh year resident and are they going to be poaching cases away from the regular residents? You know, do we have enough to go around? I mean you can’t have a IO fellow come in and take all the good IO cases and not let the residents do them. But you know–you know, you can think about it like when I was a resident, I scrubbed with the fellows all the time, right? So why wouldn’t our residents be scrubbing with our fellows? I mean, to me that just means as an attending I get to sit in the control room and do the voice of God thing on the intercom and not wear lead. Sounds like heaven. But also as to Dan’s point, like that year is not going to be spent all doing cases, right? I mean, I think an IO fellow would rotate in oncology, would rotate in surgical oncology, so they bolster their clinical experience.

Mm-hmm. .

And I think also, as you said, the research training would be a key part of it, so they’re not going to be in the lab all the time. And then of course–the big question of course is always funding. Who’s–you know, if they’re not ACGME approved spots, who’s going to pay for these fellowships? Because they’re, you know–I mean Moffitt has one and Memorial Sloan Kettering has one, but they’re paying for those for people, right? They’re usually, you know, people who are getting a free ride or something, or paying their own way. So I don’t know what your thoughts are on that.

Correct. Yeah, we actually have not an IO, but we have an advanced PD fellowship.

Oh you do?

So, just the things that you said makes sense. So are you going to take the case away from others? We don’t do it that way. That fellow serves as an instructor, is a secondary person in the room, learns, assists. It’s actually a good teaching and feedback mechanism. And we were able to integrate that into our program. Some of the candidates who come in for the PA fellowship, they don’t have overall experience, they need training and other things too. Because, you know, the variation in each practice model, every institution, in IR, is huge, so they end up doing other things too. But whatever they want to learn, they end up doing more of that by double scrubbing, et cetera. I think the clinical part of it in the IO could easily be done that way. And then as you mentioned, the other factors, you know, other learning processes, could be added to that.

Yeah, I think–I did a two year fellowship, which I think Mike also did.

Yes.

And you know, my second year of fellowship, I had a lot of cases I was doing, guiding the younger residents, and I think that’s kind of what this is. I think a lot of people that do this will be more academic dedicated and that will actually help the trainees on the other side of that year, right? Because they’re going to go out there with another year of confidence under their belt. So new attendings–I mean, they want to do well, but there’s often some happy handedness going on where they’re like, you know, anxious and excited. And I think this will help them transition and become better academic attendings as far as teaching and allowing independence of the operators early in their career.

Yeah. As you said, we’re not reinventing the wheel. I mean, I did a two year fellowship just like Dan, so my second year I was essentially functioning as a junior attending. I mean, it was mostly research, whereas when I was in the lab, like, I took the place of an attending. I like your point about making them an instructor, you know, nothing like–you know, if they’re going to function like an attending in part they should be paid like an attending in part and not be on a resident’s salary, which is really good. And there’s plenty of precedent, like in our interventional neuroradiology program, it’s two years and they’re an instructor. The second year they’re treated like junior faculty. So, you know, they’re plenty of models for doing this. I think you just have to be a little thoughtful about how you construct the curriculum to make sure you’re being fair to your residents. And of course you have to overcome the obstacle of funding. I think if it gets GME accredited, that makes it a little bit easier. But you’re still facing the problem is that the pool of funding within the institution is fixed. So if you’re going to give your GME money to your fellow, you’ve got to take it from somewhere else. So we have to think about, you know, the feeder line into the residency. You know, does this come at the price of, for example, you know, someone who’s an independent residence slot, you know?

Correct. Yeah. So that brings us to our last topic to discuss. We’ve gone over what’s going on. What do you think, Mike, in the potential new techniques and procedures in the future? What’s coming up?

Oh, that’s a very good question. You walk around the SIR meeting and you see so many exciting things in the booths, especially the little hidden booths in the back that, you know, no one else can see. So you have all these technologies. I think clearly, you know, one of the hot topics we’ve alluded to is using interventional radiology procedures as immuno stimulants. They combine with various forms of immune-based systemic therapies. So you’re seeing, you know, histotripsy, you’re seeing the pulse electrical fields, so other techniques of tumor destruction that are also, we hope, immunogenic, you know. So it’d be very–and those stuff are of course much earlier stages, but they’re being developed for delivery through, you know, endoscopes as well as through catheters, as well as through direct puncture. One of the things that we’ve been trying without much success is local delivery for CAR-T therapy.

So of course CAR-T therapy has been–worked great for liquid tumors, but has not worked well for solid tumors, because you know, you just–you know, there’s a reason why those cells aren’t in the tumors. That’s why you have cancer, you know. And so how do you get CAR-T cells that are designed to work to treat your own individual personalized cancer into those tumors? You know, because you’ve got to break down all the barriers that keep the T-cells out. So whether it’s local delivery by injection, whether it’s intravascular delivery, you know, people are trying all sorts of things and frankly they’re not working very well. So that’s a big, you know, area of opportunity that, you know–a problem we have not solved yet. Dan?

I think there’s a big opportunity in cholangiocarcinoma if MISPHEC hits. I think that’s going to change the paradigm. And those patients will be coming for local regional therapy like HCC had been in the past, because if you’re healthy and can tolerate combined therapy, that will be the standard of care. Beyond that, I think there’s a lot of opportunities in pain management. I have a pretty busy–not–you know, a growing, steady kypho practice, vertebroplasty practice, cementoplasty practice. And it’s very rewarding. I mean, people walk out an hour later and their pain’s gone. It’s awesome. But I think things like cryolysis for the thoracotomy patients with intractable pain, there’s a lot that we can do there, especially in end-stage patients approaching hospice to make them more comfortable and have a more dignified end of life period.

Completely agree. I also agree with the kyphoplasty, vertebroplasty part. We do that a lot; it’s one of the most rewarding ones. And it’s something that–you do something that–hope the patient’s going to survive longer, et cetera. You don’t see immediate gratification with the kyphoplasty you do, or pain procedures you do. It changes their life. It’s not always like how long you live, it’s how you live. You know, that’s a huge impact.

And I think that you, you know, I agree with you a hundred percent. I mean palliative care, not just pain, but other palliative procedures we do such as ascites management–I mean these are all things where massive opportunity for us to help people. Massive volume of cases that could be done. But where’s the data, you know? And it’s not like we know we can do all these things, but frankly you have to publish a paper on it to convince all the oncologists to–and the palliative care specialists–to actually send the patient to you and not just keep giving them narcotics, you know? So that’s something that we have, you know. We all do a lot of these procedures, but we haven’t actually done great research on them.

Yeah. Also to get insurers to pay for it sometimes too.

Sure. That’d be huge. You know, like for instance, you know, I don’t do the spinal stuff. I know that the results are fantastic, but I’m like–we’re very interested in our ascites program because we realize we’re doing like 500 LVPs a year and you know, when you see people coming in every month or more than that, you know, for an LVP, I mean, that’s not a life, right? That’s horrible, you know. It’s terrible palliation and it’s been, you know, studied in ovarian cancer and some other areas showing the rapid, you know, decrease in quality of life, the rapid increase in sarcopenia on people, and their life’s being sucked away from them. And yet, you know, we all have our LVP clinics where, you know, you run in, you stab–you know you’re there for five minutes–you stab in the catheter, you walk out, and then they get drained for an hour and then they call you for the next patient.

And you know, the techs are doing everything else. And who spends the 15 minutes it takes to figure out what this–some–patient needs, a TIPS or a Denver shunt–and yet you do that TIPS or a Denver shunt and–it’s like doing a kyphoplasty. I mean, they come in in a wheelchair and they walk out cheerleaders and they’re so, so happy. But you know, you mention a Denver shunt to an oncologist, they’re like, “What’s that?” Or, “Oh, you’re going to give my patient lung mets.” I was like, “That doesn’t happen.” You know, come on. But–so we need to educate, but you need–we need to educate with data.

Yeah.

So you know, thinking about each of these things and coming up with prospective trials where we’re looking at palliative outcomes as opposed to cancer–traditional cancer outcomes–would be a huge unmet need, I think.

Health-related quality of life outcomes.

Yes, exactly right.

I’m going to make one last comment. The next thing I want to see is, just like the COLLISION, you know, ablation versus surgery. But you all both know that there are certain lesions, size or location, ablation is not an option, but Y-90 ablation is an option. I wish we could do a trial, randomized, to show that as well. That’s one thing I want to see personally in the next couple years if possible. Anything else like that that you guys want to see that we should research?

Are you thinking Y-90 versus surgery or Y-90 versus ablation or a three-armed study?

Versus surgery.

I think that’s a great trial.

Yeah.

And it may not be that hard to recruit to for older patients.

Yeah.

Right? If they’re still eligible. But those are the ones that the surgeons are a little hesitant to–that may be something that could help feed enrollment.

Anything you want to add, Mike?

No, this has been a great conversation. I think we’ve sort of covered the gamut–

Perfect.

–of interventional oncology now and in the future. I mean, the great thing about it is it’s exciting, it’s fun, it’s growing, it’s always changing. I mean, it’s going to keep me working for another five years.

Awesome. Thank you everyone. I think this was a great conversation. In the 45 minutes I learned a lot. Hopefully this helped our listeners as well.

Thank you very much.

Thank you.

Thank you.