Cincinnati Children’s Hospital Medical Director and Director in the Division of Oncology, John Breneman, MD and John Perentesis, MD talk about a faster proton therapy.
Interview conducted by Ivanhoe Broadcast News in 2022.
Can you explain proton therapy?
BRENEMAN: Proton therapy as a kind of radiation therapy which is a really common tool that we use to treat cancer. But it differs from the conventional type of radiation therapy and we can steer it differently and we can control where it goes better. So it’s not that it works any better than conventional radiation, it just causes fewer side effects both during and after treatment.
How precise can it be? You talk about wanting to spare some of the other tissue, how precise is proton therapy?
BRENEMAN: So it’s something that we can steer within a couple of millimeters, depends a bit on the part of the body. We can steer it better in places that don’t move, like in the head, in and around the lungs that move it’s a little bit less precise.
And in terms of treatment, you said it’s not necessarily better, just better for the patient maybe in terms of side effects?
BRENEMAN: Yeah, better for the patient from the side effect standpoint, but it really doesn’t work any better than conventional radiation for treating the tumor.
Talk to me about the FLASH trial.
BRENEMAN: FLASH is a type of variation that is the same as the proton therapy that we give, but it’s just given much faster. So a treatment that might typically take a minute would be delivered in a half a second. The reason that- that turns out that that’s important is that in some of the laboratory work that’s been done leading up to the clinical trial, that can even further spare some of the normal tissue from the effects of radiation. So the side effects decrease with FLASH therapy, at least in the pre-clinical testing that’s been done.
Is there a percentage of how much more powerful that that radiation FLASH is than your traditional therapy?
BRENEMAN: Yeah, it’s probably not powerful because it’s the same radiation that’s just, again, much faster, but it probably has an additional 30-40% ability to spare side effects as compared to the conventional types of radiation that will do.
Is this a one and done that you’re looking at? Can you tell me a little bit about that?
BRENEMAN: Yeah, for the current trial, that’s the case now. That’s not necessarily the way it would eventually be able to be used, but currently we would be just treating one session only.
So tell me about the trial. This is the first time that it’s been tested in humans?
BRENEMAN: So we’ve completed the- the very first FLASH trial. That was completed last year, and this is the follow-up to that. So what we’re doing now with this new trial are treating different areas of the body. The first trial was done in a way that was maximizing safety. So we were just treating tumors that occurred in the arms and the legs. And this is now going to be treating tumors that are occurring in the trunk, and so we’re going to be exposing other organs in the body to FLASH radiotherapy and be able to see if there’s any unexpected toxicity or side effects.
What are the implications of having this as a therapy? Being able to administer the therapy this way.
BRENEMAN: Well, if it works the way that we hope it is going to, it’s going to decrease further the side effects of treatment. And it probably will be able to decrease the number of treatments that patients have have to have. So instead of potentially having say weeks of treatment, they could have a few days.
Let’s talk a little bit about the side effects. So what kind of things could it eliminate for patients?
BRENEMAN: That’s going to depend on where in the body or you’re being treated. But so far, it looks like every area that we’ve looked at as far as the side effects, that FLASH has the ability to decrease those.
Are you talking about just tissue damage or what kind of side effects do you potentially get from that proton therapy?
BRENEMAN: Again, it’s very specific to what area of the body you’re talking about. But in the brain, it could decrease the potential risk of having problems with learning and memory and thinking after treatment, in the chest, it would potentially decrease the injury that radiation could cause to the heart and the lungs, and in the stomach and the abdomen area to the intestines.
What are the next steps? You say you have a small population of patients you are testing right now. So where do you go from here?
BRENEMAN: So after this trial, the plan is that we would then look at actually treating tumors. It’s just a backup. Right now the tumors that we’re treating are just in bones and the chest area but the next step would be to do treatment to areas a tumor that are actually in the organs themselves like the lung.
And then from there, what’s your patient size population?
BRENEMAN: This new trial is also going to recruit 10 patients.
Where does the research go from there? Once you’ve tested in this 10 patients, what’s the next step?
BRENEMAN: Then that may be the time when we open it up to other centers and then treat these tumors that are inside the organs.
What would you want people to know about this therapy and the potential that FLASH has for treatment down the road?
BRENEMAN: Well, right now flash therapy in terms of anticancer treatment and radiation treatment is particular is- is probably the most exciting thing that we have in the field in terms of new developments.
Anything I didn’t ask you that you would want to make sure people know?
BRENEMAN: We also hope to extend the trials to- right now the trials are just for adults, but we hope to be able to extend that to children because that’s the population where we could benefit from decreasing side-effects even more.
How is this different than traditional proton therapy?
PERENTESIS: Yeah, well, to talk about flash, I think one of the things is to write set or orient proton therapy versus conventional radiation therapy. And proton therapy, particularly for kids and young adults, people in their 20s and 30s and even some older adults is a real leap frog advance for proton therapy. It’s thinking about basically what GPS and what radar did for aviation and other things. So proton itself is extraordinarily at the highest level of precision. Machines like this actually have the latest form of proton therapy, which is called pencil beam scanning. So when you actually look at what the beam is doing, looks like 3D printing. And so it’s super precise.
So when you have that machinery, are you looking at taking it to the next to the next level?
PERENTESIS: To the next level. Yeah. So proton therapy right now goes to places where surgeons can’t, is a good way to think about it. And it provides extraordinary precision. As I said, significantly ahead of the older x-ray forms of therapy. Flash is the next elevation of that technology. And what flash allows you to do is to give you the dose in one short fraction of very quickly. What that looks like it does when you test it on animals that have tumors, is that it looks like it kills the tumors really well, just like regular proton does, but it looks like it actually preserves the normal cells around it. So the normal tissues, so much less side effects, maintains extraordinarily high precision kills tumors, so safer for normal tissue. The other thing that we have some evidence for, although this is still research, is that it actually may activate the immune system to better kill the cancer cells. So a twofold direction if the research pans out to show better killing of tumors, but also much safer for normal organs.
So tell me about the trial. Are you testing this, is just for adults right now?
PERENTESIS: Right now it’s just an adult’s. New treatments always start first in adults, just because they can give good consent. And also just in case with something totally new and totally revolutionary, just to make sure there isn’t something totally unexpected. And fortunately, we completed the first flash trial and the globe right in this room, right here. And that basically showed what we had expected; good tumor control, good killing of the tumor, and really not damaging significantly normal tissue. So it was a real landmark that we’re proud of and we’re proud here at the Children’s and UC to lead that trial.
Again, some of the other differences between first delivering the therapy this way and traditional therapy. Fast, if I understand, that’s just a one and done?
PERENTESIS: Yeah. So flash the name of the trial was fast, but yeah, one and done. So it doesn’t necessarily deliver more radiation, but it delivers it 100 times more quickly. That does those two things to less damage or significantly less damage to any normal organs around the tumor, but preserves the tumor killing effect.
What are the next steps?
PERENTESIS: Yeah, it’s a good question. We’re excited about flash and the entire field is excited. And as I said, we’re particularly proud of that study. The physics community, and their trade publication named our clinical trial one of the 10 top advances in physics of the last year. So it was right up there with NASA nudging an asteroid and the web space telescope. So we’re really excited about that. We think there’s lots of potential. We’re looking at combining the fast effect with ways to modulate the immune system to see if that actually does help kill tumors that we can’t otherwise kill. And then also, when you think about it, if it kills tumors as well, preserves the normal tissue. It allows you to use more effective doses or ultimately escalate the dose of radiation in tumors that are responsive to radiation but not cured right now by radiation, and in kids, that’s a big challenge because about a quarter of kids need radiation as part of their cure for cancer. There are some cancers that we really don’t have good cures for, brain tumor or certain types of brain tumors. One called DIPG, where it responds to radiation, but we can’t give quite enough to cure it. So one research question is, will flash be able to help us cure kids with DIPG or other tumors that we can’t cure right now?
What are the implications of potentially having this down the road?
PERENTESIS: So one thing we have to learn from our research is, is the flash effect in all tissues and does it work in your brain, as well as your lungs and your bones and things like that? So one of the big opportunities and what our big research plan here is to actually define that, where does the flash effect work? Where can we use it and use it to treat and cure cancers that we can’t cure right now? So we’re focusing in our plans for research to cure kids who we don’t cure right now is to start with brain tumors, some sarcomas, lymphomas that don’t respond to therapy. So we have a roadmap of where we want to see flash and if it can transform cancer therapy.
Anything I didn’t ask you that you want to make sure people know?
PERENTESIS: I think one of the things is we want to really thank the adults who were the participants in the faster one trial. Not only was it a landmark study, and in the radiation community in the cancer community flash is one of the very top exciting topics. But these folks were courageous volunteers for a new therapy. We’re very pleased that it worked really well, but we really want to thank them. The other part is where we’re really excited about what’s going on here at Cincinnati Children’s and the university. It’s a really dynamic corridor that Cincinnati really highlights. A lot of really cool leading-edge research right here in this room, as I said and in other aspects of medicine, but it’s in a real dynamic corridor just up the road from us. Folks at GE Aviation have their headquarters and they’ve just developed jet engines that have the propulsion of the early manned rockets. So we’re real excited to be here in Cincinnati and be part of this really technologically advanced community.
END OF INTERVIEW
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Cincinnati Children’s Hospital
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cincinnatichildrens.org/proton & proton-therapy@cchmc.org
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