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

Dig Surg. 2025;42(3):136-145. doi: 10.1159/000545246. Epub 2025 Apr 14.

Abstract

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 3 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.

Keywords: Brachytherapy; Holmium microspheres; Intratumoral injection; Pancreatic cancer; Pancreatic ductal adenocarcinoma.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal* / diagnostic imaging
  • Carcinoma, Pancreatic Ductal* / radiotherapy
  • Feasibility Studies
  • Female
  • Holmium* / administration & dosage
  • Holmium* / adverse effects
  • Humans
  • Injections, Intralesional
  • Male
  • Microspheres
  • Middle Aged
  • Pancreatic Neoplasms* / diagnostic imaging
  • Pancreatic Neoplasms* / radiotherapy
  • Radioisotopes* / administration & dosage
  • Radioisotopes* / adverse effects
  • Radioisotopes* / therapeutic use
  • Ultrasonography, Interventional

Substances

  • Holmium
  • Holmium-166
  • Radioisotopes