In this study, we evaluated a total of 117 patients who had metastatic castration-resistant prostate cancer, and we treated them with actinium-targeted alpha therapy. So these patients have advanced prostate cancer and targeted radionuclide therapy with alpha particles is different from beta particles, which is very well known as Pluvicto currently. Alpha particles are greater in size, have greater linear energy, and they need less heat to kill DNA compared to beta therapy...
In this study, we evaluated a total of 117 patients who had metastatic castration-resistant prostate cancer, and we treated them with actinium-targeted alpha therapy. So these patients have advanced prostate cancer and targeted radionuclide therapy with alpha particles is different from beta particles, which is very well known as Pluvicto currently. Alpha particles are greater in size, have greater linear energy, and they need less heat to kill DNA compared to beta therapy. And also the ligand in this therapy is different. It’s an antibody ligand, has greater affinity in the prostate cancer cell, and greater retention compared to small molecule ligand. We looked at baseline PSMA PET with gallium-68, PSMA-11, and also we looked at follow-up 12 weeks after therapy with actinium-targeted radionuclide therapy. And we compared that, what we found in the images, SUV min, SUV max, and total tumor volume with outcomes. And we tried to find a correlation between the biomarkers, imaging biomarkers, and the outcomes in terms of PSA 50, that is biochemical response, overall survival mainly. What we found, so for this trial, for this project, this is a post-hoc analysis of four clinical trials at our institution, early phase clinical trials. As I mentioned previously, we included 117 patients and they had like four different clinical trials, two were single agents of actinium and two were actinium in combination with other therapies. So one of those combinations was with lutetium-177 and the other combination therapy was with pembrolizumab and androgen receptor pathway inhibitors. So in terms of results, what did we find? We found that at baseline, SUV-min and SUV-max were associated with biochemical response in terms of PSA 50. And when we looked at the follow-up images and we determined the percentage of change between baseline and follow-up, we found that total tumor volume was associated with PSA response. So the higher difference between baseline and follow-up correlated with biochemical response, like higher odds of achieving at least 50% decline in PSA. In terms of overall survival, we found that SUV mean and total tumor volume were associated with overall survival. So higher SUV means and higher total tumor volumes were associated with a protective effect, and patients had better outcomes, like they lived longer compared to lower total tumor volume and SUV mean. And at follow-up, we found that total tumor volume was associated also with overall survival. So the greater the difference between baseline and follow-up in total tumor volume was associated with longer survival. And interestingly, also we found that prior chemotherapy was associated with higher hazard ratios. And p-values were statistically significant. In terms of adverse events, because this is a very quick question from our oncologist and urologist. So we found also that at baseline, higher total tumor volumes were associated with higher grades of myelosuppression, mainly anemia. But we also found that higher total tumor volumes at baseline had lower risk of xerostomia and nausea. So what this tells us is that patients are having a PSMA antigen-specific effect that is higher than their total tumor volumes or their SUV means the targeted radionuclide therapy is going to these places and is not going to other vital organs such as parotids and glands. So this tells us about the biology of the prostate cancer and the PSMA expression and how the therapy goes to the tumor and avoids other vital organs. This is also important because now we can better select patients for this therapy. So what we are trying to prove here is that PSMA PET at baseline and follow-up can be considered a biomarker and we can better select patients both for clinical trials and eventually for treatment. Thank you.
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