Abstract：
OBJECTIVE: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial.
METHODS: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated.
RESULTS: Seven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs.
CONCLUSIONS: Radioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information.
METHODS: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated.
RESULTS: Seven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs.
CONCLUSIONS: Radioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information.
摘要：
目的：描述6个月的安全性，在首次人体试验中，成像玻璃钇-90放射性栓塞治疗不可切除的肝细胞癌（HCC）后的功效和多模态成像性方法：Eye90微球®（Eye90），FDA突破性的指定设备，是在CT和SPECT/CT上可见的玻璃不透射线的Y-90微球。在一项前瞻性开放标签试点试验中，六名无法切除的HCC患者接受了选择性（≤2段）Eye90治疗。关键纳入标准包括仅肝HCC，ECOG≤1，病变总长度≤9cm，Child-PughA.采用前瞻性分区剂量学。安全,生物化学,毒性,不良事件（AE），评估了CT和SPECT/CT的多模态成像能力以及3和6个月MRI局部改良RECIST（mRECIST）反应。
结果：6名HCC患者（7个病灶）接受Eye90治疗，随访180天。行政成功率为100%。90眼CT射线不透性分布与SPECT/CT相关。在6名受试者中观察到3名（50％）的目标病变完全反应，在2名（33.3％）中观察到部分反应。在180天不能评估两个受试者。180天,目标病变完全缓解3例(50%),部分缓解1例(16.7%).所有受试者报告了AE，5例报告与治疗相关的AE。没有治疗相关的严重AE。
结论：Eye90在6名不可切除的HCC患者中安全有效，长达6个月。眼睛90可通过CT和SPECT/CT成像，CT射线不透性与SPECT/CT放射性分布之间存在相关性。Eye90提供了以前无法获得的基于CT的肿瘤靶向信息。
结果：6名HCC患者（7个病灶）接受Eye90治疗，随访180天。行政成功率为100%。90眼CT射线不透性分布与SPECT/CT相关。在6名受试者中观察到3名（50％）的目标病变完全反应，在2名（33.3％）中观察到部分反应。在180天不能评估两个受试者。180天,目标病变完全缓解3例(50%),部分缓解1例(16.7%).所有受试者报告了AE，5例报告与治疗相关的AE。没有治疗相关的严重AE。
结论：Eye90在6名不可切除的HCC患者中安全有效，长达6个月。眼睛90可通过CT和SPECT/CT成像，CT射线不透性与SPECT/CT放射性分布之间存在相关性。Eye90提供了以前无法获得的基于CT的肿瘤靶向信息。
