Supplementary Material for: 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.

引言
胰腺导管腺癌（PDAC）预后极差，且缺乏局部治疗方案。本研究旨在评估首次在人体中实施的术中超声引导下放射性钬-166微球瘤内注射治疗PDAC患者的可行性与安全性。
方法
纳入经证实的PDAC患者，这些患者符合开放手术切除条件。若术中探查时放弃切除，则实施研究干预措施。可行性通过注射成功与否及靶向/脱靶辐射情况来定义。安全性基于12周内不良事件（AE）监测结果，按严重程度分级及研究相关性分类。
结果
13例纳入患者中有3例接受了研究干预。所有3例患者的注射均成功完成。肿瘤平均剂量分别为5.0、17.0和39.0 Gy，最大肿瘤剂量分别为25.0、41.0和256.0 Gy。脱靶辐射各出现1次（肺部和结肠），平均剂量均<1.0 Gy。未发生与研究高度相关的不良事件（AE）；与研究低度相关的AE分别为16、14和19例，其中包括3、2和4例≥3级的AE。钬-166微球在CT上呈现高密度影。
结论
对于不可切除的PDAC患者，瘤内注射钬-166微球似乎具有可行性与安全性。建议开展关于微创影像引导应用的研究。