Treatment or low-grade meningiomas with helium, proton and carbon ions: Optimization of treatment planning, establishment of study concepts and in vivo verification

即使在现代放射肿瘤学中，良性和恶性脑肿瘤的治疗仍然是一个挑战。粒子疗法提供了独特的物理和生物学特性，可能有助于提高脑肿瘤治疗的风险-收益比。在该项目的前期资助期内，已经计划、启动了颅底脊索瘤和软骨肉瘤以及原发性胶质母细胞瘤的研究，目前正处于招募阶段。在直接比较质子和碳离子的随机试验中对这三个实体进行了评估（见中期报告）。除了在上一轮项目中资助的这项工作外，该小组还对颅底脑膜瘤的治疗进行了广泛的审查，包括生物学，物理学和临床方面。更新项目的目标是发展新的概念，以颗粒治疗和颅底肿瘤的体内验证，特别关注低级别和高级别脑膜瘤。现有治疗方案的优化将首先通过与现有质子和碳离子束以及氦束模式的治疗方案比较来进行研究，这些治疗方案将在我们的设施中可用。将特别强调减少毒性和辐射引起的危险的可能性，这反过来又与剂量递增研究有关。这些比较不仅涉及由现有的商业或研究处理计划系统（tps）提供的吸收和生物RBE（相对生物有效性）加权剂量，而且还将包括有关量的详细比较，如剂量平均线性能量转移（LET）和中子剂量，这可能由专门的蒙特卡罗模拟提供。此外，在MIRANDA irb批准的临床研究框架内，通过辐照后基于正电子发射断层扫描（PET）的治疗验证的前瞻性应用，将解决高剂量一致性和减少周围关键结构负担的临床可行性。因此，第一个临床目标是为脑膜瘤患者提供最优化的粒子治疗方案。不同的工作包涉及放射治疗的重要步骤，从最佳治疗计划开始，特别是在引入新光束（如氦束）时，靶体积定义，临床数据的回顾性评估，为后续临床研究提供重点，减少治疗时间（低分割）以及最小化毒性。

Treatment of benign and malignant brain tumors remains a challenge even in modern radiation oncology. Particle therapy offers distinct physical and biological characteristics potentially contributing to an improved risk-benefit-ratio for the treatment of brain tumors. In the previous funding period of the project studies on skull base chordomas and chondrosarcomas, as well as on primary glioblastomas have been planned, initiated, and are currently in the recruitment phase. All three entities are evaluated within randomized trials directly comparing protons and carbon ions (see Interim Report). Besides this work funded within the previous round of the project, the treatment of skull base meningiomas has been reviewed extensively including biological, physical and clinical aspects by the group. The goal of renewal project is to develop novel concepts for treatment with particle therapy as well as in-vivo verification of skull base tumors with special focus on low- and high grade meningiomas. The optimization of existing treatment options will be first of all investigated by means of treatment plan comparisons with the already existing proton and carbon ion beams as well as the helium beam modality which will be available at our facility. Special emphasis will be given to the possibility of reducing toxicities and radiation induced risks, which could in turn be connected to dose escalation studies. These comparisons will not only involve absorbed and biological RBE (relative biological effectiveness)-weighted dose as provided by available commercial or research treatment planning systems (TPSs), but will also include detailed comparison of relevant quantities such as dose-averaged linear energy transfer (LET) and neutron dose which may be provided by dedicated Monte Carlo simulations. Moreover, the clinical feasibility of high dose conformality with reduced burden to surrounding critical structures will be addressed via prospective application of post-irradiation Positron-Emission-Tomography (PET)-based treatment verification within the framework of the MIRANDA IRB-approved clinical study. Thus, the first clinical goal is to provide optimized treatment concepts with particle therapy for patients with meningiomas. The different workpackages address the important steps in radiation therapy starting from optimal treatment planning, especially when introducing novel beams such as the helium beam, target volume definition, retrospective evaluation of clinical data for a subsequent clinical study focusing on reduction of treatment times (hypofractionation) as well as minimization of toxicity.