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The OPuS One Study: Advancing Clinical Evidence in the Treatment of Bone Metastases

The OPuS One Study: Advancing Clinical Evidence in the Treatment of Bone Metastases

The OsteoCool™ RF Ablation System is a cooled radiofrequency ablation technology that offers simultaneous dual-probe capabilities for treating painful bone tumors. Outcomes on the first 100 patients treated with the OsteoCool™ System from the OPuS One Study were recently published in the November edition of the Journal of Vascular and Interventional Radiology (JVIR). This ongoing, multicenter, post-market study is the largest prospective study on radiofrequency ablation for bone metastases. IO Learning spoke with Jason Levy, MD, lead investigator of OPuS One, to learn more about the study results.

[PODCAST TRANSCRIPTION]

Ami Peltier [00:00:06] Hi, and welcome to IOL Radio. I’m Ami Peltier, managing editor of IO Learning, a digital publication geared toward interventional oncologists, and the news source for the symposium on Clinical Interventional oncology. In this episode of IOL Radio, we’ll discuss Medtronic’s OsteoCool radiofrequency ablation system, which is a cooled RFA technology that offers simultaneous dual-probe capabilities for treating painful bone tumors. Outcomes on the first 100 patients treated with the OsteoCool™ System from the OPuS One Study were recently published in the November edition of the Journal of Vascular and Interventional Radiology. This ongoing, multicenter, post-market study is the largest prospective study on RFA for bone metastases. I spoke with Dr. Jason Levy, interventional Radiologist at Northside Hospital in Atlanta, Georgia and lead investigator of OPuS One, to learn more about the study results. Thank you for joining us to discuss the Opus One study, Dr. Levy. 

Jason Levy [00:01:12] Thanks for having me. 

Ami Peltier [00:01:16] Let's start by discussing the technology behind the OsteoCool radiofrequency ablation system. How does it differ from currently used ablation technologies?

Jason Levy [00:01:24] So, essentially there's three ablation technologies that are commonly used in the market today — one a little less commonly, certainly in bone applications — and that's microwave which is an interesting technology. It is also heat-based like RFA; however, it is less well tested, and my only concern about microwave is it does and will cross some osseous borders more easily than radiofrequency ablation will, so that's the least commonly used. The more commonly used technologies are RFA and cryoablation. And there are different benefits to both. In the OPuS One trial, this was a palliative setting, and it was for osseous metastases in essentially the axial skeleton. So, we were talking about the pelvis and we’re talking about the spine. So, we're talking about weight-bearing bones. And while you can, with cryoablation, put cement in after, it is much more challenging and you typically don't get the even cement fill. So, you minimize one of the advantages of the treatment and that is the cement that we use after the ablation, so that's one of the challenges with cryoablation. The other challenge with cryoablation is that — similar to microwave and even moreso — one of the things we know about RFA for better or worse is radiofrequency ablation energy will not cross (or will not cross as well is a better way of saying it) osseous intact borders. So the effect is dampened by that, while there is really no effect on cryoablation. So that's both good and bad.

Jason Levy [00:03:15]  So, in a setting where you're treating with a palliative intent, obviously you want to do no harm, and if a cryoablation method will potentially cross an osseous border, you are running more risks, especially posteriorly in the spine that is, so you can get a nerve injury more likely with cryo. So that's sort of the two challenges with cryo. That's not to say that I don't think cryo has a huge component in this space and a huge role in this space. This space really needs to open up for all interventional radiology, and it's something that we need to be doing much more, and I think cryo will play a big role in that setting, especially because of how well it does in soft tissue. 

Jason Levy [00:04:08]  But then we go to RFA energy, and RFA energy is sort of a great, simple, easy-to-use, very available technology that in this setting in the OPuS One trial really provided the best of all worlds. So, one of the things we know about RFA energy is that it has been shown that it creates a cavitary effect. So, put simply, it makes basically a hole in the bone that makes it easier and a more even cement fill afterward. So again, it's sort of speaks to the ease of the second part of the procedure, which is augmenting the bone with cement to prevent fractures and prevent a delayed skeletal event. The technology used in the OPuS One trial was cooled technology, meaning it's internally cooled so, you know, sort of a misnomer “OsteoCool” — we know we're ablating with heat and we're killing tissue with heat, but the “cool” part is the internal cooling that prevents charring at the tip of the probe. So, the challenge with charring — which is when we have non-cooled devices, which are also out on the market — is the charring creates an effect of minimizing the RF energy. So, it's sort of like if you cook a steak on a grill and you just have it frozen but you turn it up to 700° — what you're going to have is a burnt outside and it's still frozen inside. So you're essentially not getting the heat distal to where the tip is.

Ami Peltier [00:05:53] Which types of patients stand to benefit from OsteoCool therapy, and how does this technology compare with the current standard-of-care for bone metastases?

Jason Levy [00:06:04] So, it's going to be used more often in the palliative setting and you know, RFA in the palliative setting is frankly well-established and this trial really just adds to a well-established treatment that is underutilized. It certainly also can be used and should be used with more of a curative intent in settings of oligometastatic disease with fewer than 3 or 4 or even 5 metastases, where your intent is different — where your intent is to eradicate the disease. There certainly are trials out there — retrospective trials — looking at the curative intents with oligometastatic disease. Most of those trials use multiple different energies and are looking at a retrospective dataset. But the most common application for this will be in a palliative setting where we're treating patients, treating their pain, and treating their their disability and sometimes their inability to get their systemic therapy. So, which patients will benefit the best? The sort of “home run” for this is patients with lytic metastatic disease or a lytic component of metastatic disease in weight-bearing bones, so that would be the spine, the sacrum, the pelvis, basically and I think that's where you're going to see the most benefit for these patients in that setting. And again, that goes back to our ability to cement afterward. So one of the key points from this study was the lack of delayed skeletal events. So when I say delayed skeletal events, I mean things like new nerve injuries or fractures, so that's kind of our home run. 

Jason Levy [00:08:10] So how does that compare to what is out there? So really what is out there, you're talking about for the most part you're talking about radiation. So, radiation is a proven and established therapy. However, it has some shortcomings and the beauty of this procedure is it sort of takes care of almost all of the shortcomings and does not exclude radiation afterward. So, shortcoming number 1 is the time for pain relief, right? So, the time for pain relief is usually between 4 to 6 weeks. The time for pain relief in OPuS ONE was 3 days, which is obviously a huge difference, especially when you take into account how much life these patients have left to live.

Jason Levy [00:09:05] The second difference is, many times with radiation, patients have to come off of their systemic therapy. With ablation, we don't stop anything — maybe blood thinners, but that's it. There's no holding of systemic therapy. And then third is the delayed skeletal events. So, I just told you that delayed skeletal events happen after treatment of osseous metastases, but we saw none in our trial, and that was really essentially related to the use of cement. You won't find a radiation trial that shows that. In fact, there have been trials on SBRT [stereotactic body radiation therapy] that have shown anywhere from 11% to 39% fracture rate after their treatments and those were from major medical centers such as MD Anderson, Sloan Kettering, and Sunnybrook.

Ami Peltier [00:09:05] So, you mentioned a little bit about the OPuS One study. Can you tell us more about it and describe the primary objective of the study and take us through the methodology?

Jason Levy [00:10:11] Absolutely. So the intent of the study was really to further establish radiofrequency ablation as a safe and effective treatment for musculoskeletal metastases, and really hopefully to start utilizing this therapy more whether as a stand-alone therapy or in combination with radiation. So, we enrolled patients with 1 or 2 sites of disease that needed treatment. Now that doesn't mean that they only had 1 or 2 sites of disease, but there couldn't be more than 2 sites of disease causing the patient's pain, okay, or causing the majority of the patients pain.

Jason Levy [00:10:55]  We enrolled patients, they had to have a lytic component. They could not be entirely blastic, so that excluded a lot of the prostate cancer patients, but we do know that some prostate cancers will have lytic component, so a few of them were included in the study. The primary endpoint was the worst pain in the last 24 hours at the 3 month time period. So, we followed patients up at 3 days, 1 week, 1 month, 3 months, 6 months, and then if available 12 months. The results were statistically significant for pain relief at the worst pain, the average pain, quality of life indices, and we measured those at each and every data point and those were statistically significant at each and every one. So obviously a a very successful trial.

Ami Peltier [00:12:00] Can you tell us a little bit more about the results? Did you see any side effects or adverse events? 

Jason Levy [00:12:06] Sure, so, as I stated earlier, we did not see a single delayed skeletal event, which in this patient population is huge. There were a few adverse events and I'm going to sort of separate those out. So, a fair number of deaths occurred in the first 100 patients, I believe it was about 30 deaths. But that was evaluated by an independent interventional radiologist who was not part of the study, and those were deemed to be related to the patient's underlying condition rather than the procedure itself, so not really a true adverse events. It more spoke to the fact that we were seeing these patients, unfortunately, so late in their disease, which is something that we would like to see in the future, where we can get these patients a little earlier and get a better benefit. The patients were expiring related to their underlying condition. There were small adverse events related to respiratory problems that happened within the first couple of days after the procedure, and there was only 2 of those in the first 100 patients, but no deaths or grade 4 or 5 adverse events occurred in this patient population, so a very low complication rate or adverse effect rate. 

Jason Levy [00:13:37]  The only thing I did leave out about the patient population, which really made this somewhat of a unique trial, is most of the radiofrequency ablation — or really, frankly, percutaneous ablation trials in the past — have had confounding results related to the use of radiation. So, at the time of treatment, this was surprisingly a very radiation-naive population. So only 5% of the patients actually had radiation before this was done, and we know that with radiation, most series show a success rate (overall response rate) of about 60%. So, you would have expected to see a higher number of failures coming into the trial, but we did not see that many, which was surprising, but was useful in that we know that it was the ablation that created our results. In addition, in the follow-up, only 14% of patients actually had radiation after. Now, this is certainly a therapy that can — and many times should — be combined with radiation. But again, from the purposes of this study, it was nice to see that it was such a low number and that again we can speak to the fact that it was the radiofrequency ablation procedure that created the excellent results rather than having it muddied by a secondary therapeutic procedure.

Ami Peltier [00:15:21] Great, so you mentioned you were surprised by some of these results. Would you say that OsteoCool has exceeded your expectations at this point? 

Jason Levy [00:15:31] Yeah, I mean, I think that the thing that was the most surprising was not that it was significant at 1 week, 1 month, 3 months, 6 months — I think we all knew that was going to happen, and I think that was not so much of a surprise. I think the big surprises were the 3 day — the fact that we were seeing improvement at 3 days. So anyone who does ablation knows that sometimes patients’ pain will get worse before it gets better. So I always warn my patients in my clinic before I treat them that there is the possibility that your average pain will go from an 8 to a 10 for a couple of days before it starts going down. So, I don't worry too much if that's happening, and that can happen, but the fact that we had significant results already at the 3-day time point was really, really encouraging, so that was you know, probably the biggest surprise to me. I mean, I'm obviously a proponent of the therapy, but even that was was a surprise to me. I guess the only other surprise was really the lack of adverse events, and when you're talking about related adverse events, what you're really talking about is a delayed skeletal event — a fracture, a nerve injury, significant neuropathy. And the lack of those was very, very encouraging.

Ami Peltier [00:17:08] Is OsteoCool therapy widely available at this point either in the U.S. or other areas to the world?

Jason Levy [00:17:15] It certainly is. I am very happy to say that its use is increasing each year quite a bit, which is nowhere near where we should be, based on results like this in a palliative setting. I still think there is a huge open market for interventional radiologists and doctors to treat patients with musculoskeletal metastases, but it is widely available across the United States. It is used in multiple hospitals certainly in my city, in cities across the country, and it is absolutely available in other countries as well. In fact, of the 16 sites that were enrolling patients, there was a Canadian site and a couple of European sites. So yes, it is available and we've spoken to physicians in South America and it's being used in I believe all continents.

Ami Peltier [00:17:08]  What future studies would you like to see done on the OsteoCool device? 

Jason Levy [00:18:22] Well, we're actually right now looking at our full dataset. So, this study that was just published was actually our first 100 patients. The study is no longer enrolling, but we were able to accrue 212 patients, so we will be publishing our results, or hopefully publishing our results, on that dataset, which will include the first 100, but be further and more inclusive of all these patients with good follow-up up to six or even 12 months on many of them. It would be wonderful to see a prospective trial on oligometastatic disease for more of a curative intent. So again, like I said, this was a palliative intent, it would be great to see a prospective trial on oligometastatic disease. The challenge is there are so many different neoplasms, so you end up, do you make this oligometastatic disease for all neoplasms — something that the radiation oncologist have done for SBRT — or do you make this isolated to, say, breast cancer mets or prostate cancer mets. So that's one of the challenges behind doing that, but we definitely need to get more data out in the curative setting, because we really do a great job in the curative setting and it’s definitely underutilized in oligometastatic disease. 

Jason Levy [00:19:53] As far as the palliative setting goes, it would certainly be nice if we could do a trial comparing radiation to a combination of this with radiation. So, like I said earlier, this doesn't exclude radiation after OsteoCool is done and I think that is one of the problems that many doctors have in trying to grow this service is a little bit of a barrier from radiation oncology that may see this as a disruptive technology, but the reality is there is actually decent data that the combination of the two may provide better outcomes for patients, and there are certainly patients that really absolutely should be getting both, and like I said earlier, the two therapies oftentimes can be very complementary and some of the weaknesses in each can be overcome by combining the two. So I do think that if we had prospective trial comparing radiation to radiation with OsteoCool, we would see tremendous benefit and would probably really shift the paradigm of patients getting treated with this therapy.

Ami Peltier [00:21:23] Did you have any final thoughts or anything else that you wanted to add about OsteoCool or about the OPuS One study?

Jason Levy [00:21:29] I think the only thing is, is that obviously these are very encouraging results, you know, as interventional radiology has progressed in the intervention oncology world, we are starting to do more — a lot more — in the liver, we’re doing a lot in the kidney, we’re doing some in the lung. I really think that we have such growth opportunity in musculoskeletal metastases, and it is really, of all of the interventional oncology things we do, this is the most untapped and we really should be aggressive about this as a society. We have so little penetrance when you look at what patients are getting referred to — radiation versus something like radiofrequency ablation. And I think as more studies like this come out, that should be changing and we should be seeing these patients earlier and we should be treating more patients and frankly getting better outcomes because of the lack of delayed skeletal events, better-paying outcomes. And really we need to get the radiation oncologists to see this as something not as a threatening technology, but as something that is actually going to help their patients and help their technology and make everyone feel better, because patients really do well as we saw with our results.

Ami Peltier [00:23:05] Absolutely, and congratulations to you and your study partners on these impressive results in the first 100 patients, I look forward to seeing the complete trial data in the coming months. And that concludes our podcast with Dr. Jason Levy. I’d like to thank Dr. Levy for meeting with me to discuss the OsteoCool Radiofrequency Ablation System and the results of the OPuS-One trial, as well as Medtronic, manufacturers of the OsteoCool System, for sponsoring this episode of IOL Radio. You’ll find further information on the OsteoCool System, including a CME opportunity, as well as other episodes of IOL Radio at www.iolearning.com. Thank you for listening!


Related CME Opportunity

Utilizing Radiofrequency Ablation to Treat Metastatic Bone Disease: A Case-Based Presentation

Matt Callstrom, MD, PhD; Jonathan Morris, MD; MK Jesse, MD; Jason Levy, MD

1.00 A+ ARRT
1.00 AAPA
1.00 CME
1.00 CNE
1.00 Participation

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