Melanie Cole, MS (Host): [00:00:00] Welcome to the podcast series from the specialists at Penn Medicine. I'm Melanie Cole. And today, we're highlighting low-dose radiation for osteoarthritis. Joining me in this panel that we have for you today is Logan Barnes, he's a physician assistant. And Dr. John Plastaras, he's the Vice Chair of Clinical Research at Penn Medicine.

Thank you both for being with us today. And Dr. Plastaras, I'd like to start with you for just a little bit of a table setting for us. How did low-dose radiation therapy break onto the scene as a treatment modality for conditions other than cancer?

Dr. John Plastaras: Thank you, Melanie, for the question. I think it's a confluence of three things that happened around the same time, because these treatments have been given for decades in Europe, Germany, in particular. So, it's nothing really new to the [00:01:00] world, but certainly is new to the US.

So, there was a review article published by Austin Dove from Vanderbilt that really got everyone's attention. It was published in our main journal, and everyone started asking questions about, you know, should I implement this in my own clinic? So, that was step one. But I think there's some bigger forces out there.

I think that there's been a real surge in alternate treatments for osteoarthritis. A lot of patients who may have taken OxyContin for their osteoarthritis have been steered away from that. So, there's a big push from [00:02:00] the folks who take care of these patients to look for alternatives. And all those three things together have really come to a head and our organization, ASTRO, has really made a push to explore this. And last year's meeting was actually dedicated to the use of radiation therapy for non-malignant conditions.

Host: Well, thank you for telling us about that. So Logan, give us a little bit of a background on the types of patients you're seeing for low-dose radiation therapy. What joints are you treating? Tell us a little bit about it.

Logan Barnes: Thank you for the introduction and for the question. So, we are seeing patients with osteoarthritis that's refractory to conservative management. We're really looking for patients that have tried oral medication, physical therapy, cortisone, hyaluronic acid injections, other types of injections. And they still have symptoms, they still have limited function. We're treating all joints except the spine. So, shoulder, elbow, wrist and hand, hip, knee, ankle, and feet.

Host: Logan, what other less common conditions are you treating with this?

Logan Barnes: So with low-dose radiation therapy, we are also treating plantar fasciitis, refractory to other conservative measures. A little bit less commonly, with moderate dose radiation therapy, we are treating Dupuytren's contracture and Ledderhose disease, which is also known as plantar fibroma.

Dr. John Plastaras:  In addition to some of the historic non-malignant conditions that Logan mentioned, the Dupuytrens, the Ledderhose, we are seeing an interest in treating other types of tendinopathies and bursitis in the functional radiation medicine community. Certainly, as a clinician, I would like to see a little more data, but I think the data for plantar fasciitis are actually pretty good. So, you know, right now, I think Logan and I mostly are treating patients with osteoarthritis [00:05:00] and plantar fasciitis. Those are our kind of top two diagnoses.

Host: Well, Dr. Plastaras, tell us how the experience of LDRT in patients with OA differs from that of patients with advanced cancers. Do they have a CT simulation, for example? Tell us a little bit about that, but I'd also like you to tell us how they're liking it and what your outcomes are like.

Dr. John Plastaras: I'll be completely honest, I was quite a skeptic about the use of low-dose radiation therapy for osteoarthritis. The data that were initially out there were mostly retrospective in nature and the small randomized trials that had been done and maybe not done perfectly well, were not all that convincing.

But more recently, we have seen a really nice trial out of Korea that made me feel like, there are some reasonable science behind the impact if you sort of carefully select your patients. But I will tell you just on a [00:06:00] personal note, it does really seem to work and when patients who have really tried everything get a treatment or two and they're feeling better and they come up and hug you, it does feel very real and I think this actually is an effective treatment.

It is quite different though from treating patients with cancer. These patients certainly are more sensitive, I think, to copays, as a lot of the other treatments out there all may have certain copays associated with them. Cancer patients usually just jump right in and do whatever needs to be taken. But I think our patients are certainly looking at this from a cost sensitivity side.

And they also look at it in terms of effort. You know, how many times do I have to come? And as you asked, our process is still pretty much the same. We start with a consultation. We bring them back for a CT simulation. So, that's another day. And then, we do our planning, which can take up to a week or so. And then, when they come back for the actual treatment, it's going to be six different visits to us, given twice a week. [00:07:00] So, it can be accomplished over three weeks. But it is quite a bit of back and forth for patients who are used to just going in, getting an injection to their knee, and going about their merry way.

Host: Yeah, thank you for that. So, Dr. Plastaras, sticking with you for a second. It's been studied several times in the past in patients with OA with inconsistent results. However, the outcomes of a Korean study presented at the Fall 2025 American Society for Radiation Oncology annual meeting were unique in this regard. So, what were the findings of the trial, and what do you feel distinguished it from earlier investigations of LDRT in OA?

Dr. John Plastaras: I think the trial was important in that it did a sham treatment, so absolutely zero treatment. Then, they compared it to two other doses. So, 3 Gray, which is the typical dose that we use, which is 0.5 Gray times six. And then, they had this other interesting arm, which is 0.3 Gray in six fractions. [00:08:00] So, they set this up as a three-arm study.

The other thing that they did really well is they limited the patients who could enter to having what I would call a moderate osteoarthritis of the knees. So, there is a scale called the Kellgren-Lawrence scale that looks at how bad the osteoarthritis is, and they did not enroll patients who had a 0 or 1, and they did not enroll patients who had a 4. They only looked at the twos and threes. So, those are the patients in between. And I think that was really important in terms of their criteria.

And then, the other thing that they did is they actually kept patients from taking anything other than Tylenol. So, there was a fairly good scientific look at what the impact was of the low-dose radiation on its own without being interfered by other medications such as narcotics or NSAIDs.

So, I think that really distinguished it and led them to see an improvement rate in the 3 Gray arm of around 70% compared to the sham arm, [00:09:00] which was about 40%. So, that was pretty convincing and quite statistically significant. Interestingly, the 0.3 Gray arm was numerically superior to the sham arm but was not statistically significant. So, it does seem that even teeny-tiny doses might have an impact. We're still learning about that for sure, and there's a lot of preclinical work that we're actually doing at Penn to try to explore some of those concepts.

Host: Well, to expand on that, Doctor, I understand you'll be starting a clinical trial with a grant from the Radiation Oncology Institute. Tell us about that trial and its main objectives.

Dr. John Plastaras: The trial that we're planning on starting this summer is a prospective trial where we are going to treat patients with osteoarthritis, regardless of location, so all the locations that Logan mentioned. We will be collecting additional quality of life instruments. So, we're going to be looking at pain, but not just a simple pain score. We're going to be looking at a multidimensional pain score. We'll also be looking at [00:10:00] functional scores that will then break down into upper and lower halves of the body. So, we're really going to see how this impacts not just pain, but also function.

And the thing that I think is most interesting about it is that we are doing this in a population that has not been studied well before. So, the patients who are on the Korean trial and those patients who are treated in Germany, have tended to be the older types of patients. But I'll tell you, the patients that we're seeing are patients who may be what we call metabolically inflamed. So, they might be, overweight, they may have diabetes or pre-diabetes. So, these are a different group of patients, and we're really curious to see if low-dose radiation works well in that metabolically inflamed population.

And then, one other very interesting subgroup that we're excited about is patients who have breast cancer, who may have preexisting osteoarthritis, but go on medications called aromatase inhibitors, which have a high risk of causing musculoskeletal pain. Up to 20% of patients with [00:11:00] breast cancer who are taking these life-saving medications actually have to stop due to their pain. We're hoping to enroll a certain portion of those in this study to see if low-dose radiation can actually impact the joint pain that those patients experience.

Host: That's so interesting. So finally, Logan, where is the Penn Functional Radiation Program situated? Who is it comprised of? Tell us a little bit about how the efforts are coordinated with those of the orthopedic division and referring physicians.

Logan Barnes: This program is centered at Penn Presbyterian Medical Center, here in West Philadelphia. The team is comprised of myself, Dr. Plastaras, other radiation oncologists, Dr. Michelle Iocolano, and Dr. Eva Berlin. They'll be helping out with these research studies that Dr. Plastaras mentioned. In addition, we have a program [00:12:00] coordinator named Diamond, who is kind of the main contact point for scheduling. And of course, I can't forget our other parts of the research team, our wonderful nurses, and our radiation therapy team here. Within the Penn system, referrals can be made directly to our team by placing a radiation oncology consult, and then there's a specific option for the osteoarthritis program that will direct patients to Diamond to help get on the schedule. Physicians referring from outside of the system will also use Diamond as a contact point, and we are also open to self-referrals.

Dr. John Plastaras: And I'd like to add something if I can, the Penn Medicine Radiation Oncology Network [00:13:00] actually expands across the region. We have sites in Cherry Hill, Doylestown, Radnor, Valley Forge, Chester County Hospital, and other locations that all are able to deliver this low-dose radiation therapy.

So, what we'd like to have is Logan and one of my partners at Penn Presbyterian see the patient first, even if that's by telemedicine, and then we can make recommendations, and then those treatments can be carried out closer to these patients' homes. And I think this is really important for these diagnoses, because the patients may have mobility problems. So if they can go five minutes down the street to Doylestown to get their treatment, then that's really a win for the patient and also for the health system providing that care.

Host: Thank you both so much for joining us today and telling us about this really interesting new therapy. Thank you again. And to refer your patient to Penn Medicine, please call our 24/7 provider-only line at 877-937-PENN, or you can submit your [00:14:00] referral via our secure online referral form by visiting our website at pennmedicine.org/refer. That concludes this episode from the specialists at Penn Medicine. I'm Melanie Cole.