Martin King: Okay. Really, thank you for the invitation. I'm excited to share the three results of the Barrigel™ randomized trial evaluating hyaluronic acid spacer for hypofractionated prostate radiation therapy. I was the coordinating investigator for this study and I've also had grant funding from Teleflex as well as other companies. And this is just a really short outline of my talk. I'll just talk with the introductions, the methods, results, and then a quick conclusion.
So over the past decade, there has been increased utilization of moderately hypofractionated radiation therapy. These are radiation regimens that occur over a four to five and a half week time span. And we can see from the graphs on the top that for both low and favorable intermediate-risk disease, the percentage of patients getting moderately hypofractionated radiation therapy as evidenced by the grade line has been increasing with time. However, moderately hypofractionated radiation therapy has been associated with more acute GI toxicity. And this was nicely shown in a meta-analysis of phase three randomized trials showing that compared to standard fractionated radiation therapy, up to 10% of patients may be at greater risk of a Grade 2 acute GI toxicity.
And so we sought to evaluate whether a stabilized hyaluronic acid rectal spacer could decrease the chance of acute Grade 2 or higher GI toxicity. And so between 2020 and 2021, we conducted a randomized trial in which patients were randomized to the presence or absence of hyaluronic acid spacer. The randomization was two to one and every patient received 60 Gray in 20 fractions. Patients were stratified by the presence or absence of ADT, erectile quality, good versus poor, as well as geographic region since this was a multinational trial. And you can see in the images on the right, you can see the potential effect of rectal space around radiation planning. For the images without Barrigel™ rectal spacer, you can see how the 50% isodose line, this would be about 30 Gray radiation, goes right through the rectum. However, when the spacer is in place on the right-hand side of images, you can see how that 50% isodose line goes through the spacer, thus less radiation dose to the rectum.
And so in our early results, which we have already reported, we showed that 98.5% of patients achieved a greater than 25% reduction in the rectal V54 Gray, and so we hit our primary endpoint. We also showed that rectal spacers also reduced the risk of acute Grade 2 or higher GI toxicity. And the numbers were 2.9% for the spacer arm versus 13.8% for the control arm. And we have published these results back in 20 and 23.
So for the current study, we were interested in seeing whether the hyaluronic acid rectal spacer reduces late Grade 2 or higher GI or GU events. And so what we wanted to do was just to look at outcomes up to the 36-month time point, and this was really when we stopped data collection. We looked at three specific aspects. One aspect was dosimetry. We wanted to see the percentage of patients who had what we called optimal rectal dosimetry based on analysis of the CHHiP trial. Patients who achieved these constraints actually had better bowel quality of life than patients who did not. We also wanted to look at the cumulative incidences of late Grade 2 or higher GI or GU toxicities across treatment arms. Finally, we wanted to see the percentage of patients with differences in bowel MCID or a minimally clinically important difference in bowel quality of life at 36 months across the treatment group.
So in terms of our results from the dosimetric aspect, we actually saw that most patients on both arms actually had optimal dosimetry that met CHHiP constraints and these constraints once again were associated with better bowel quality of life. As expected, we could see that the dosimetric values, the mean dosimetry for patients who had the rectal spacer as shown in the light blue was better or lower than patients on the control arm. We did note that there were six patients who had late Grade 2 or higher GI toxicity and their DVH curves are highlighted in red. And what we can see is that five out of the six patients actually had worse rectal dosimetry compared with the mean value for the control arm.
We looked in our toxicity outcomes a little bit more clearly. We were able to estimate that about 9.5% of patients in the control arm had late Grade 2 or higher GI toxicity versus 0% in the spacer arm. We also looked at the cumulative incidences for GI toxicity as shown on the two graphs on the upper right and upper mid. And we can see that for Grade 1 or higher GI toxicity, there was a significant difference favoring the spacer arm. We also saw that for late Grade 2 or higher GI toxicity, there was a significant difference across curves that favor the spacer arm. Regarding genitourinary toxicity, we did see a benefit for the spacer for late Grade 1 or higher GU toxicity, but we did not see a significant difference for late Grade 2 or higher GU toxicity.
We also wanted to look at the potential impact of bowel quality of life across spacer arms. And so we had about 151 patients or 76% of patients had submitted EPIC best questionnaires at baseline and at 36 months. And as you can see in the curves on the right, there was no significant difference in terms of bowel quality of life between the control arm or the spacer arm. In both curves, the higher number is better, lower number is worse. We also calculated the percentage of patients with an MCID or minimally clinically important decline. And what we saw was that the valleys were 31% for the control arm versus 21% for the spacer arm and there was no difference in terms of the percentage of patients across the entire time period. We then did some further analysis. In a couple prior publications, we had reported that apical spacing, which is the distance between the prostate and the rectum at the most inferior slice of the prostate was associated with better bowel quality of life at three months.
In the images on the bottom left, you can see that this is a patient who has pretty adequate apical spacing, so greater than or equal to 10 millimeters, and an apical level is highlighted in orange. And you can see that the 40-Gray isodose line or the 50-Gray percent isodose lines are through the spacers or at just the very anterior tip of the rectum, whereas for patients who have less than 10 millimeter apical spacing as shown on the image on the right, you can see that all those high isodose lines really go through the anterior portion of the rectum. So what we did was we took the spacer arm and we subdivided them into greater than or equal to or less than 10 millimeter apical spacing. And what we were able to see was that when we looked at just the subgroup of patients with greater than or equal to versus less than 10 millimeter apical spacing, there was improved bowel quality of life for patients with more apical spacing.
These patients, as highlighted in the blue curve, also had fewer patients with an MCID and bowel quality of life. And when we compared them across treatment arms, we actually saw a potential benefit in the subgroup of patients with more apical spacing. So in summary stabilized hyaluronic acid rectal spacer was associated with durable reduction in late Grade 2 or higher GI toxicities despite excellent contemporary rectal dosimetry in the control arm and rectal spacing may provide the greatest patient-reported benefit when implant geometry achieves adequate apical separation.
So I'd like to thank all of the patient participants, all of the site participants who worked hard to get the patients on the study, the core laboratory, also members who were very involved in data analysis as well as the sponsor. Thank you very much.
Zachary Klaassen: Martin, thanks so much. Great data, great presentation. I should mention this was presented at ESTRO 2026 in Sweden in the spring. What's interesting is if you look at the spacing market now, it's getting quite busy, but this is the first three-year toxicity data for rectal spacer in a clinical trial. So how does this three-year toxicity, in your opinion, as a radiation oncologist, as a key opinion thought leader in this space, how does this separate Barrigel™ from some of the other rectal spacers on the market based on having this extended follow-up data?
Martin King: Yeah, I think that what makes this trial specifically unique is that it was the first trial that really focused on hypofractionated radiation therapy. And as we know over the past 10 years, there's really been a gravitation from conventional to moderately hypofractionated and more patients are even getting ultra hypofractionated radiation, but this study really shows the potential benefit of rectal spacing for patients receiving moderate hypofractionation. And I think that does set the clinical evidence behind the Barrigel™ hyaluronic acid spacer.
Zachary Klaassen: No, that's great. I think one thing that's interesting too is I know initially this trial wasn't designed to show GU improvement in toxicity, but we did see a Grade 1+ improvement at that six to 36 months. What do you make of that improvement in GU toxicity?
Martin King: Yeah, I think that it is something that we did observe. I think that it is something that's quite interesting. And I think the question is as well, is there a dosimetric explanation for it? And currently we don't have a dosimetric explanation for that. My hunch is that maybe by having that rectal spacer, they can keep some of the high-dose regions off of the bladder neck or have a more homogeneous plan over the urethra, but we would certainly be interested in looking into that a little bit more to see if we can find dosimetric predictors of GU toxicity.
Zachary Klaassen: Sure. Fantastic data. Again, any take-home messages, anything we haven't hit on that you want to share with our listeners before we wrap up?
Martin King: I think that I'd just like to reemphasize the point that rectal spacing does decrease the risk of both acute and late GI toxicity, Grade 2 or higher. The number of patients with these toxicities, it is quite low, but if you do have a patient with this toxicity, it can be actually life altering in terms of multiple visits to the gastroenterologist, potential interventions. And so I think that this helps lend support to using rectal spacing for reducing the risk of significant GI toxicity, which could be problematic for patients who have that.
Zachary Klaassen: Absolutely. Martin, thanks again. Always enjoy chatting with you. Thanks for sharing your time on UroToday.
Martin King: Okay. Thank you so much.