Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
Radiat Oncol. 2022 May 25;17(1):102. doi: 10.1186/s13014-022-02070-x.
Stereotactic Body Radiotherapy (SBRT) is a standard treatment for inoperable primary and secondary lung tumors. In case of ultracentral tumor location, defined as tumor contact with vulnerable mediastinal structures such as the proximal bronchial tree (PBT) or esophagus, SBRT is associated with an increased risk for severe complications. Magnetic resonance (MR)-guided SBRT can mitigate this risk based on gated dose delivery and daily plan adaptation. The MAGELLAN trial aims to find the maximum tolerated dose (MTD) of MR-guided SBRT of ultracentral lung tumors (ULT).
MAGELLAN is a prospective phase I dose escalation trial. A maximum of 38 patients with primary and secondary ULT with a tumor size ≤ 5 cm will be enrolled. Ultracentral location is defined as an overlap of the planning target volume (PTV) with the PBT or esophagus. Patients are treated at a 0.35 Tesla MR-linac (MRIdian® Linac, ViewRay Inc. ) employing a gating strategy and daily plan adaptation. Dose escalation starts at 10 × 5.5 Gy (biologically effective dose BED: 155.83 Gy/85.25 Gy), may proceed up to 10 × 6.5 Gy (BED: 205.83 Gy/107.25 Gy) and is guided by a customized time-to-event continual reassessment method (TITE CRM) with backup element, which alternately assigns patients to dose escalation and backup cohorts.
The results of the MAGELLAN trial will guide further research and clinical implementation of MR-guided SBRT as ablative treatment of ULT. Moreover, the combination of MR-guided radiotherapy with TITE-CRM including a backup element may serve as blueprint for future radiation dose escalation studies in critical locations.
Registered at ClinicalTrials.gov: NCT04925583 on 14th June 2021.
立体定向体部放射治疗（SBRT）是治疗不可手术的原发性和继发性肺肿瘤的标准方法。对于超中心肿瘤位置，定义为肿瘤与脆弱的纵隔结构（如近端支气管树（PBT）或食管）接触，SBRT 与严重并发症的风险增加相关。基于门控剂量递送和每日计划适应性，磁共振引导 SBRT 可以降低这种风险。MAGELLAN 试验旨在确定超中心肺肿瘤（ULT）的磁共振引导 SBRT 的最大耐受剂量（MTD）。
MAGELLAN 是一项前瞻性的 I 期剂量递增试验。最多将招募 38 名原发性和继发性 ULT 患者，肿瘤大小≤5cm。超中心位置定义为计划靶区（PTV）与 PBT 或食管重叠。患者在 0.35 特斯拉磁共振直线加速器（MRIdian® Linac，ViewRay Inc.）上接受治疗，采用门控策略和每日计划适应性。剂量递增从 10×5.5Gy 开始（生物有效剂量 BED：155.83Gy/85.25Gy），可能进展到 10×6.5Gy（BED：205.83Gy/107.25Gy），并由定制的时间事件连续再评估方法（TITE CRM）指导，该方法交替将患者分配到剂量递增和备份队列。
MAGELLAN 试验的结果将指导磁共振引导 SBRT 作为 ULT 消融治疗的进一步研究和临床实施。此外，将 MR 引导放疗与包括备份元素的 TITE-CRM 相结合，可能为未来在关键部位进行放射剂量递增研究提供蓝图。
于 2021 年 6 月 14 日在 ClinicalTrials.gov 上注册：NCT04925583。
