Intratumoral Holmium-166 Microsphere Injection in Patients with Unresectable Pancreatic Ductal Adenocarcinoma: a Single-Center, Single-Arm, Open-Label Feasibility and Safety Study.

Introduction Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks local treatment options. This study aimed to assess the feasibility and safety of the first-in-human intraoperative ultrasound-guided intratumoral injection of radioactive holmium-166 microsphere in patients with PDAC. Methods Patients with proven PDAC eligible for open surgical resection were included. If resection was abandoned during exploration, study intervention was performed. Feasibility was defined by injection success and on/off-target radiation. Safety was based on adverse event (AE) monitoring for 12 weeks categorized by severity grade and study attribution. Results Three of the thirteen included patients received study intervention. Injection was successful in all three patients. Mean tumor doses of 5.0, 17.0 and 39.0 Gy and maximum tumor doses of 25.0, 41.0 and 256.0 Gy were achieved. Off-target radiation was found once in the lungs and once in the colon with a mean dose <1.0 Gy. There were no AEs with high study attribution, 16, 14 and 19 AEs with low study attribution, including 3, 2 and 4 AEs with grade ≥3. Holmium-166 microspheres appeared hyperdense on CT. Conclusion Intratumoral injection of holmium-166 microspheres in patients with unresectable PDAC seems feasible and safe. Research into minimally invasive image-guided application is advised.