Motion management for real-time adaptive MRgRT in liver and rectal cancer

本项目的目的是在1.5 T MR-Linac混合系统中研究肿瘤在照射期间（内抽吸）和部分之间（干涉）的运动。这种混合装置可以通过基于解剖和功能MRI的个体化剂量处方促进新的和创新的治疗策略的发展。这在肝肿瘤中特别有趣，因为肝肿瘤周围的健康肝组织通常是剂量限制的，而在直肠肿瘤中，为了提高完全缓解率和促进器官保存，计划增加剂量。然而，由于呼吸（肝脏）或直肠和膀胱充盈的变化，这两个肿瘤部位都是移动的目标。因此，高度精确的个体化剂量处方的先决条件是评估肿瘤内和肿瘤间的运动。在本项目中，我们将建立一个优化的1.5 T MR-Linac的四维成像方案，包括解剖和功能成像序列。在此基础上，我们将开发一种立体定向体放射治疗（SBRT）的4d反应适应方案。这个想法是根据放射引起的肝脏疾病（RILD）的发展风险和在各部分之间的解剖和功能成像上看到的反应来个性化剂量处方。对于直肠癌，目标是评估整个肿瘤的癌内和癌段间运动，以及可能作为“bioBoost”靶点的潜在亚体积。这个bioBoost亚体积是通过扩散加权成像观察到的变化来定义的，这已经被证明是肿瘤消退的预测。在这个项目中，我们将利用治疗过程中评估的可用成像数据进一步完善这些模型，并测试不同的bioBoost策略，如顺序增强或立体定向综合增强。开发的方法将导致前瞻性介入试验，测试4D运动校正磁共振引导适应性放疗的概念。

The aim of this project is to investigate tumour motion during irradiation (intrafraction) and between fractions (interfraction) at the hybrid 1.5 T MR-Linac system. Such a hybrid device may facilitate the development of novel and innovative treatment strategies by individualized dose prescriptions based on both anatomical and functional MRI. This is particularly interesting in liver tumors where the surrounding healthy liver tissue is often dose limiting and in rectal tumors when dose escalation is planned in order to increase complete response rates and facilitate organ preservation. However both tumor sites are moving targets due to respiration (liver) or changes of rectal and bladder filling. Thus, a pre-requisite for highly precise individualized dose prescriptions is the assessment of the intrafractional and interfracional tumor motion. In this project we will establish an optimized four-dimensional imaging protocol for the 1.5 T MR-Linac with both anatomical and functional imaging sequences. Based on this we will develop a 4D-response-adaptive protocol for stereotactic body radiotherapy (SBRT) of liver tumors. The idea is to individualize the dose prescription based on the risk of the development of radiation induced liver disease (RILD) and the response seen on anatomical and functional imaging between fractions. For rectal cancer the goal is to assess intrafractional and interfractional motion of the entire tumour and of potential subvolumes that might serve as targets for a “bioBoost”. This bioBoost subvolume is defined by changes observed on diffusion weighted imaging which has already been shown to be predictive of tumor regression. In this project we will further refine these models with the available imaging data assessed through the course of treatment and test different bioBoost strategies such as a sequential boost or a stereotactic integrated boost. The developed methodologies will result in prospective interventional trials that test the concept of 4D motion corrected MR guided adaptive radiotherapy.