Goal: This study evaluates the feasibility and outcome of a personalized MRI-based liver SBRT treatment planning platform with the SPION contrast agent Ferumoxytol®(Sandoz Inc.; Princeton, NJ, USA) to maintain a superior real-time visualization of liver tumors and volumes of functional hepatic parenchyma for radiotherapy planning throughout multi-fractionated liver SBRT with online plan adaptations on an Elekta Unity 1.5 T MR-Linac (Elekta; Stockholm, Sweden). Materials and Methods: Patients underwent SPION-enhanced MRI on the Elekta Unity MR-Linac for improved tumor and functional hepatic parenchyma visualization. An automated contouring algorithm was applied for the delineation and subsequent guided avoidance of functional liver parenchyma volumes (FLVs) on the SPION-enhanced MR-Linac. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were assessed with at least 6-month radiographic follow-up. Pre- and post-transplant outcomes were analyzed in the subset of patients with HCC and hepatic cirrhosis who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease (MELD-Na) was used to score hepatic function before and after SBRT. Results: With a median follow-up of 23 months (range: 3–40 months), 23 HCC patients (26 lesions treated) and 9 patients (14 lesions treated) with hepatic metastases received SBRT (mean dose: 48 Gy, range: 36–54 Gy) in 1–5 fractions. Nearly all patients in this study had pe-existing liver conditions, including hepatic cirrhosis (23), prior TACE (7), prior SBRT (18), or history of hepatic resection (2). Compared to the non-contrast images, SPIONs improved tumor visibility on post-SPION images on the background of negatively enhancing functionally active hepatic parenchyma. Prolonged SPION-contrast retention within hepatic parenchyma enabled per-fraction treatment adaptation throughout the entire multi-fraction treatment course. FLV loss (53%,p< 0.0001) was observed in cirrhotic patients, but functional and anatomic liver volumes remained consistent in non-cirrhotic patients. Mean dose to FLV was maintained within the liver threshold tolerance to radiation in all patients after the optimization of Step-and-Shoot Intensity-Modulated Radiotherapy (SS-IMRT) on the SPION-enhanced MRI-Linac. No radiation-induced liver disease was observed within 6 months post-SBRT, and the MELD-Na score in cirrhotic patients was not significantly elevated at 3-month intervals after SBRT completion. Conclusions: SPION Ferumoxytol®administered intravenously as an alternative MRI contrast agent on the day of SBRT planning produces a long-lasting contrast effect between tumors and functional hepatic parenchyma for precision targeting and guided avoidance during the entire course of liver SBRT, enabling fast and accurate online plan adaptation on the 1.5 T Elekta Unity MR-Linac. This approach demonstrates a safe and effective bridging therapy for patients with hepatic cirrhosis, leading to low toxicity and favorable transplant outcomes.
目的：本研究旨在评估基于个性化磁共振成像（MRI）的肝脏立体定向放射治疗（SBRT）计划平台的可行性与疗效。该平台采用超顺磁性氧化铁纳米颗粒（SPION）造影剂Ferumoxytol®（山德士公司；美国新泽西州普林斯顿），在Elekta Unity 1.5 T磁共振直线加速器（Elekta；瑞典斯德哥尔摩）上进行多分次肝脏SBRT治疗期间，通过在线计划调整，实现对肝脏肿瘤及功能性肝实质体积的持续优质实时可视化，以优化放疗计划。 材料与方法：患者在Elekta Unity磁共振直线加速器上接受SPION增强MRI检查，以提升肿瘤和功能性肝实质的可视化效果。应用自动勾画算法，在SPION增强的磁共振直线加速器图像上勾画功能性肝实质体积（FLV），并据此指导放疗计划避开这些区域。放疗剂量限制仅针对FLV进行调整。通过至少6个月的影像学随访评估局部控制率、毒性反应及生存情况。对于完成SBRT作为肝移植桥接治疗的肝细胞癌（HCC）合并肝硬化患者亚组，分析了其移植前后的结局。采用终末期肝病模型（MELD-Na）评分评估SBRT前后的肝功能。 结果：中位随访时间为23个月（范围：3-40个月），23例HCC患者（治疗26个病灶）和9例肝转移患者（治疗14个病灶）接受了1-5分次的SBRT（平均剂量：48 Gy，范围：36-54 Gy）。研究中几乎所有患者均存在既存肝脏疾病，包括肝硬化（23例）、既往经动脉化疗栓塞术（TACE）（7例）、既往SBRT（18例）或肝切除史（2例）。与非增强图像相比，SPION在功能性活跃的肝实质背景呈负性增强的背景下，提高了SPION增强后图像中肿瘤的可见性。SPION造影剂在肝实质内的长时间滞留，使得在整个多分次治疗过程中能够进行每次分次的治疗调整。在肝硬化患者中观察到FLV减少（53%，p < 0.0001），但非肝硬化患者的功能性和解剖性肝脏体积保持一致。在SPION增强的MRI直线加速器上优化步进式调强放射治疗（SS-IMRT）计划后，所有患者的FLV平均受照剂量均保持在肝脏放射耐受阈值范围内。SBRT后6个月内未观察到放射性肝病，且肝硬化患者的MELD-Na评分在SBRT完成后每3个月的间隔期均未显著升高。 结论：在SBRT计划制定当天静脉注射SPION Ferumoxytol®作为替代性MRI造影剂，可在整个肝脏SBRT疗程中，在肿瘤与功能性肝实质之间产生持久的对比效果，从而实现精准靶向和引导避让，并支持在1.5 T Elekta Unity磁共振直线加速器上进行快速、准确的在线计划调整。该方法对肝硬化患者而言是一种安全有效的桥接治疗策略，具有低毒性和良好的移植结局。
肿瘤(癌症)患者之家