Implications of the Yttrium-90 Glass Microsphere Tumor Dose Analysis for Interventional Radiology

Transcript:

Juan Gimenez, MD: I think the main result of the study—what we were able to do—is just to show that we replicated what was published by some of the other landmark large trials showing the effectiveness of radiation segmentectomy. The significance of radiation per microsphere, or specific activity, is that it's ultimately one of the most important factors associated with CPN, or complete pathologic necrosis, which is ultimately associated with better outcomes and improved overall survival down the line. I think that as we grow to understand the concept of specific activity, we can better tailor how we treat patients and improve our outcomes. What is important, also regarding specific activity as it pertains to a number of microspheres, is that there's heterogeneity to the vascular supply of tumors that cannot be overcome regardless of how many particles you put in. Specific activity basically translates to how many hits of radiation the tumor cell, or the tumor DNA, can get, which ultimately results in cell death that would allow the tumor to die. It's important to understand that if one wants to achieve better outcomes and better results rather than packing more spheres into a heterogeneous area, we may need to increase the specific activity. So, we increase the number of hits or micro bullets—as my partner Dr Sandow likes to refer to them—in order to achieve, ultimately, cell death.  

As I mentioned a few minutes ago, there are landmark studies in the form of RASER and LEGACY in which the threshold dosimetry and radiation segmentectomy were proven, and I think there are datasets and our study allows us to show users the results can be reproduced regardless of the institution particularly if one has some technique and follows the dosimetry guidelines that are widely available. As I said, it's of great importance that we were able to replicate these studies and show that radiation segmentectomy is a viable treatment option for patients with HCC. Additionally, I want to add that we did look at specific activity, or radiation per microsphere, and that allows us to further hone into the technique of radioembolization. There's a lot of variability between centers and different people, particularly with newer users. So, everything that we can do to better provide guardrails and guidelines for people to be able to treat so we can all achieve the same results. It is very important.

As far as the limitations of the study, I would say it was a retrospective study. We did have about 56 patients, so it wasn't a very large study. Every time that you go into looking at voxel-based dosimetry to understand radiation, there are going to be some spatial resolution limitations, particularly SPECT/CT. So, I would just say that, probably, those were some of the limitations, and when we look to truly understand how many particles per cc can be delivered in our study, it was not really designed for that. So, we probably need to conduct additional studies to look at that information.  

I think we have a good understanding of the roles that radiation per microsphere and specific activity play in the treatment algorithm for HCC. I think it'd be important that we continue to educate the interventional radiology community so that they can understand how to utilize that concept so that they can optimize their treatment algorithms and parameters. With that being said, based on the available literature and what we found in our study, treating with glass microspheres anywhere, with no later than 8 days post calibration, will be what we would recommend to optimize your outcomes. I think there probably needs to be still a little bit more of an understanding of the role that particles play. We do understand that tumors are heterogeneous and that heterogeneity cannot be overcome despite how many particles we add. That has been shown in animal research, it's also been shown—we found that in our study—and in other studies available in the literature that despite no matter how many particles you add, you're still not able to overcome that heterogeneity, and you don't create additional clusters.  

So, optimizing the overall radiation dose and the number of hits you deliver, particularly to the areas that do not have as much vascularity, they are what we like to call colder, is extremely important. I think there needs to be a little bit more research on that front, and I would say to add some on how we approach some of the larger tumors, even though some of that data is actually starting to come out as well.  

What I've seen when treating patients with glass Y90 is that when done appropriately—taking into account all the parameters that we discussed—particle load, specific activity, and overall radiation dose—this is a very safe modality with a very minimal amount of adverse events. That's something we actually showed in our study, which is very well tolerated by patients and provides excellent outcomes with improvement or extension in overall survival.