Feasibility, safety and efficacy of endoscopic ultrasound-guided alpha radiotherapy for advanced pancreatic cancer: A pilot study.

721 Background: Pancreatic cancer (PDAC) is a devastating disease with limited locoregional treatment options. Diffusing Alpha-Emitter Radiation Therapy (Alpha DaRT), a novel alpha-emitting radiation source, has demonstrated safety and efficacy in the treatment of superficial epithelial solid tumors. The current trial studied the application of this treatment modality to PDAC for the first time. This innovative approach involves the interstitial implantation of Alpha DaRT in pancreatic tumors using endoscopic ultrasound (EUS). Methods: This single-arm, open-label trial (ClinicalTrials.gov Identifier NCT04002479) enrolled patients with inoperable locally advanced (LA) or metastatic (M) PDAC at two tertiary care centers in Montreal, Canada. The primary objective was to assess the feasibility and safety of EUS-guided Alpha DaRT delivery to the target tumor, and the secondary objective was to evaluate best overall response of the primary tumor using Response Evaluation Criteria in Solid Tumors version 1.1. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events version 5. EUS-guided Alpha DaRT placement was confirmed by CT. Overall survival was evaluated using Kaplan-Meier survival analysis. Results: A total of 32 patients (13 male, 19 female), median age 73 (range: 41-91), were enrolled from 2023-2024. Fourteen patients had LA-PDAC and 18 had M-PDAC. The median follow-up was 6.2 months. Successful placement of Alpha DaRT sources in or around the pancreas tumor was achieved in all cases (100%). A total of 52 device-associated adverse events (AEs) were observed in 13 (41%) patients, with 49 grade 1-2 and 3 grade 3 AEs. Two AEs (biliary obstruction and bacteremia) were deemed to be serious AEs, both of which subsequently resolved. Tumor response data were available for all 32 treated patients. 81% demonstrated disease control (DCR), of which 73% (19) had stable disease, 15% (4) had partial response, and 12% (3) had complete response, yielding an overall response rate (ORR) of 22%. Excluding the first two patients who had low, sub-optimal Alpha DaRT delivered for safety run-in, the DCR and ORR were 87% and 23%, respectively. Median overall survival was 17.0 months across all subjects to date, evaluated from last chemotherapy (17.5 months when excluding the two patients in the run-in cohort). Conclusions: EUS-guided alpha radiotherapy with Alpha DaRT is a technically feasible and safe treatment of pancreatic cancer, with encouraging local disease control in this first-in-human trial. Additional studies to further assess the efficacy of this promising novel modality in specific patient subpopulations are underway. Clinical trial information: NCT04002479 .