背景:局部晚期非小细胞肺癌(LA-NSCLC)患者通常不适合手术,因此,确定性放化疗(CRT)代表了治疗的选择。然而,肿瘤的长期控制往往无法实现。增强放射治疗(RT)以改善局部肿瘤控制受到胸部危险器官(OAR)较高辐射暴露的有害影响的限制。可以通过利用磁共振(MR)线性加速器的优点来扩展这种狭窄的治疗比例。主要是根据每日采集的MR图像对当前解剖结构进行在线调整。然而,MR指导既是劳动密集型的,又增加了治疗时间,这引发了其治疗LA-NSCLC的临床可行性问题。因此,PUMA试验被设计为前瞻性的,多中心I期试验,以证明MR引导的在线自适应RT在LA-NSCLC中的临床可行性。
方法:30名IIIA-C期LA-NSCLC患者将在三家德国大学医院接受两种不同MR-直线加速器系统的MR引导在线自适应RT(MRIdianLinac®,ViewRayInc.和ElektaUnity®,ElektaAB)同时进行化疗。应用具有高达70Gy的等氧剂量递增的常规分割RT。在线计划适应每周一次或在重大解剖变化的情况下进行。治疗后24个月对患者进行胸部CT和MR成像随访。主要终点是双重的:(1)成功完成在线适应分数,(2)上桌时间。主要次要端点包括自适应频率,毒性,局部肿瘤控制,无进展生存期和总生存期。
结论:PUMA旨在证明MR引导的LA-NSCLC在线适应性RT的临床可行性。如果成功,PUMA之后将进行临床II期试验,进一步研究这种方法的临床益处。此外,PUMA是开发MR指导技术的大型多学科项目的一部分。
背景:ClinicalTrials.gov:NCT05237453。
BACKGROUND: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA
trial was designed as a prospective, multicenter phase I
trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC.
METHODS: Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival.
CONCLUSIONS: PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II
trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques.
BACKGROUND: ClinicalTrials.gov: NCT05237453 .