My name is Krishnan Patel and I'm one of the radiation oncologists at the National Cancer Institute. Today I am pleased to present the results of NCT03253744: "A Phase I Trial of Salvage SBRT for Radiorecurrent Prostate Cancer After Brachytherapy" on behalf of our study team. In this trial, dose escalation commenced in parallel across two cohorts. The first which is the topic of the present discussion, profiles treatment for radio- recurrence, post-brachytherapy and the second previously published profiles salvage SBRT after initial external beam radiation therapy. Next, we will review the baseline characteristics of patients on this arm at initial diagnosis, approximately three quarters of men had favorable risk disease with the remainder having unfavorable intermediate risk disease. All patients underwent treatment with brachytherapy with the majority of their initial courses direct to the prostate alone and a single patient undergoing brachytherapy as part of a treatment plan including pelvic irradiation. At enrollment most patients had relatively low PSAs given that most were screened shortly after the diagnosis of biochemical failure. Lastly to contextualize the toxicity outcomes of this trial, the majority of patients had grade 1 GU toxicity at baseline with a single patient being free of all gradable GU toxicities prior to treatment. Each patient underwent a course of SBRT delivered in five fractions at least 48 hours apart. To a treatment volume defined by two dose levels, including an elective treatment volume defined by the prostate and involved seminal vesicles with the margin and a boost volume defined by the GTV plus 3 to 5 millimeters. Image guidance was used prior to each fraction in between each arc. Pictured here is a summary of the maximum toxicity experienced by each patient in this cohort. The first two patients were treated on Dose Level 1 and no DLTs were observed. Each experience self-limited acute GI toxicity lasting for less than 10 days and, contrastingly, each experienced grade 2 GU toxicities lasting from 5 to 10 months in duration. Thus, dose escalation proceeded to Dose Level 2. Similarly, the second three patients were treated without the observation of DLT. The GI toxicity again was minimal with one patient having a two-day period of self-limited diarrhea and, similarly to the first cohort, all participants experienced a maximum of grade 2 GU toxicity. While no DLTs were observed to this point, dose escalation was halted, due to the observation of a clinically significant burden of grade 2 GU toxicities observed in all patients in the context of promising early biochemical control outcomes. Thus, a three patient expansion cohort was treated at Dose Level 2. Again, the GI toxicities were acute and self-limited and all patients experienced a maximum of grade 2 GU toxicity. As alluded to, the biochemical control and this cohort was favorable as compared to prior series. A single biochemical failure was noted in a patient with the highest PSA nadir. Finally, imaging response was evaluated on MRI and PSMA-based PET/ CT at six months. All lesions showed a volumetric MRI response at six months with the majority of lesions showing a corresponding response in maximum linear extent in the axial plane. Similarly, the distribution of each quantitative PET measurement was observed to have a significant reduction at six months from baseline. All lesions were shown to have a response on all measurements with the exception of one lesion, shown here in green, PET volume increased slightly at six months by 0.12 CCs. In conclusion, the maximum tolerated dose for local salvage SBRT after brachytherapy was considered to be 42.5 Gy in five fractions. In this arm, while no grade 3 events were observed, the most common toxicity was grade 2 GU toxicity occurring in all patients. Contrastingly, GI toxicity was minimal and self-limited. Oncologic outcomes were promising with a biochemical progression- free survival of 86% at a median follow- up of 22 months. And finally, radiographic response on a per-lesion basis was frequent. Although further follow-up is required to investigate if early imaging response is a predictor of local control. Thank you very much for your attention and please feel free to check out our manuscript for further details.
