Phillip Koo: Welcome to UroToday. We are here today at Tulane University Cancer Center, taking a look at the various components that it takes to run a successful theranostics program. We are very fortunate to have with us today, Dr. Kendra Harris, who is the Chair of Radiation/Oncology at Tulane. And we are going to start off this segment by looking at a hot lab and looking at the various pieces that you need to operate a theranostics program. So, Dr. Harris, thank you very much for hosting us today. Can you talk to us about the various pieces of equipment that you have had to purchase in order to do the Lutetium-177 PSMA therapies?
Kendra Harris: Yeah, absolutely. So when we participated in the VISION trial, there was a bit of learning as you go. One of the things that we found was that the Geiger counter that we had used in the department for radiation safety perspective was over reading, sort of, the dose levels because it wasn’t selected for the beta and gamma. So we actually bought a 451P ion chamber to help us more accurately assess the output from men after they were dosed. That helped us develop our release levels and patterns. We also, having delivered radium out of this hot lab, had to go and get sort of a beta-specific syringe shield, as we were preparing to give lutetium in a large number of doses. We additionally bought lead aprons, lead glasses, and there has been this discussion back and forth about… there are certain groups in other countries that do not use very much in the way of shielding at all… In a question of sort of Bremsstrahlung.
So we are actually undertaking some empirical experiments to see inside or outside of those shielding opportunities. Do we measure a difference? Right now, our policy is to wear lead; lead aprons lead glasses, and then the beta shield. Part of the challenge was figuring out how to safely get the medication out of the bottle it arrived in and into a syringe that we could use for administration. So these nuke med needles were actually the key to doing that safely. We also then sort of made adjustments to our shielded area. Since, as I may have mentioned, the vials come in these, what we refer to as pigs, extra shielding. They come in like a vial, a glass vial, and we have to get all of the 10 to 12 milliliters out.
We also made this little lead igloo to help us safely move the dose from the hot lab over to the CT room. And then finally, we actually initially started in exam rooms for administration like you would do with radium, but found that the CT room just offered a more appropriate level of shielding for the betas.
Phillip Koo: I guess any room, I guess, with some shielding in the walls built to certain specifications, I imagine would be sufficient for this therapy.
Kendra Harris: Well, as I said, we started in clinical exam rooms because we were able to block off the entire hallway. So during the trial, which required hours of monitoring, we had to pay attention to the fact that these men needed to use the bathroom. And since the lutetium is cleared through the urine, that urine was highly radioactive. And in order to create a safe environment for those men to wait, we blocked off a bathroom and blocked off the hallway. And in so doing, we were able to have the men wait in clinical exam rooms.
When we opened the expanded access program here at Tulane, having given, I don’t know, 80 or 90 of these injections and having a very high level of confidence that, you know, if we have the men void before we dose them, that we can dose them and release them within 15 or 20 minutes. That allowed us to have multiple injections on the same day, use the CT scanner room for all of them, because there is throughput, and not have to put an entire hallway on lockdown for the day.
Phillip Koo: That’s great. I think a lot, that whole bathroom issue brings up a lot of fear and it’s great that you guys have figured out a way to get patients in, have them void so that the need to use the restrooms is not there. That being said, I imagine there are some cases where you perform this procedure in patients who are incontinent or have some bladder issues where they might have to use the restroom. So can you talk a little about your SOPs regarding that?
Kendra Harris: Sure. First of all, we do a careful assessment for it at the time of consult. So certainly verifying that men have adequate blood counts is the most important component of suitability, is part of the assessment. But I didn’t realize at the start, it was very important to understand, ‘are you fully continent? Do you use liners? Do you use pads?’ And so that is a very important part of the consultation before we actually come in for dosing. For men who are not fully continent, we had talked about placement of Foleys during the trial but became concerned that you could put the Foley in, but you might get urine stranded in the middle of the urethra, which may not be great from a dosing standpoint. And then you would generate a lot of radioactive waste. What would you do with these catheter bags full of radioactive urine, etc.? So we moved instead to a system where men who were not fully continent, we would have discussions about the use of pads. And then those pads would be disposed of in red bags and have them do their last change before they left.
But even so, the challenge of keeping men in the clinic for a really long time is, we had one patient who lost his outfit because the pad overflowed and there was urine on his clothing. And another reason is that since it is safe to dose these men and have them leave immediately, there are other important benefits.
Phillip Koo: Yeah, absolutely. I think the idea of the sort of shortening the stay in the department actually has a lot of benefits for multiple reasons that, which you’ve covered. So in general, Tulane Cancer Center obviously has been a leader with regards to radiopharmaceutical therapies, especially radium-223. Can you talk a little bit about that transition from a hot lab or a facility that dealt with alpha particles to now shifting to beta emitters and sort of the logistics and costs associated with that transition?
Kendra Harris: The new ion chamber measurement device I mentioned was about four grand and then when you put together a beta shield, maybe you have to buy some additional lead blocks. You have lead glasses perhaps, and various other small things. We are talking about maybe an additional $1,000 in addition to the $4,000 Geiger counter.
The other consideration is that with the betas… with the alphas, you don’t worry nearly as much about staff exposure or really at all. And we had to manage staff expectations and worries because obviously, I am doing 120 of these injections, so I’m leaded up. The staff sees that, and they’re like, “oh my God, there must be some nuclear event happening over there”. So we had to do staff engagement and education. I had three in-services with all the nurses, both to share the excitement that it’s amazing that men can come here and get this… this really impacts people’s lives, and we should be very proud of Dr. Sartor and the whole team’s work.
And it also allowed me to address some of their concerns and explain ‘why is it that I have elected to wear lead’. And that is a difference. I also offered basically to remove the IVs for any of these patients after the injection is done. I have some nurses that just, would rather not be closer if they do not have to. And that’s totally doable.
Phillip Koo: Sure.
Kendra Harris: No big deal.
Phillip Koo: That’s great. So I think clearly it shows that a lot of preparation is key, and a lot of education is key as well, even for staff and obviously for patients as well. Radiation safety is always one of those hot topics that really sparked a lot of fear in people in general. Can you talk a little bit about some of the preparations or the plans you had in place for certain radiation safety events that might occur through Lutetium-177 PSMA?
Kendra Harris: We have, as I mentioned, given over 100 injections and happily not had a safety event. We have learned some things over time. For example, initially, we weren’t putting chux pads on the floor and then during one of the administrations, as I was getting screened to leave the room, somehow a drop had gotten on my shoes and I lost that set of shoes. So we started putting chux pads over the floors and chux pads on the seats. So we did that for the next set of injections.
And we actually found that the hospital didn’t have enough hot decay space. We started generating bags of red waste that were enormous for all of these injections and all of a sudden the rate-, the RSO for the hospital said, “we are at the limit of what we can allow decaying away”. So we had to come back in and really define what chux are important. Are we being very thoughtful about what we are allowing to be counted as contaminated? Because it’s a major change from the amount of radioactive waste overall, that we had really no need to let decay. That was a big piece.
Another big piece was just getting the radiation safety committee to okay the clinical trial in the first place. Obviously, most hospital non-clinical physicists may really regard radioactive iodine as the principal isotope that they need to know about. And the idea that we now have targeted, PSMA targeted, cancer cell-targeted radioactive isotope delivery, and how that changes our consideration of the risks to the red [inaudible], to the organs, and whether or not the tools that we’ve historically used to consent people for therapy makes sense in a targeted radiotherapy environment. The total integral body dose will depend not just on the person’s total burden of a number of cancer cells, but also on the number of PSMA molecules expressed on the surface per cancer cell and the proportion of those cells exposed to the bloodstream that will allow for binding.
And so this idea of an absolute average dose that you’re arguing is true, it’s a very difficult set of arguments that had to be made over time to get this critical therapeutic to men who were dying. That took repeated meetings, education, there’s really not very much published. So sending published literature about it is hard to put your hands on. We have found, as we now have many, many, many trials open, other trials, that each time we have gone back, it gets easier and easier as we build capacity and expertise even among the hospital partner that we have.
Phillip Koo: That’s great. So thank you very much for your time and for sharing your expertise with all of us today. I think one of them, there are a lot of key lessons I think we take away from this. It’s interesting. I think one of the themes here is in terms of physical space and capital costs, it’s actually very, very low. And the message that I’m hearing is most of what you need to do is really sweat equity. It’s really investing in people and education and training that will really create a successful program. So thank you very much for sharing with us and spending your time.
Kendra Harris: Thank you.