NAPTA: Optimizing clinical trial design & delivery of particle therapy for cancer

 描述(申请人提供)：超过一半的癌症患者接受了最终放射治疗(RT)，通常是通过X光检查。具有低线性能量转移(LET)质子的粒子束放射治疗(PBRT)越来越多地被使用，因为人们认为它们可以减少并发症和改善局部控制。例如，使用碳离子的高LET PBRT可以提供比低LET RT更多的物理剂量分布优势。此外，碳和霓虹灯可能产生更高水平的抗辐射和低氧(低氧)肿瘤细胞的有效性，这代表了最具放射和化疗抗性的侵袭性肿瘤细胞。患有晚期肺癌、头颈部、脑、食道和胰腺肿瘤的成人患者可能特别受益于高LET离子的优势，但到目前为止进行的研究还不确定。为了证明开发具有高LET离子的昂贵的PBRT设备的合理性，需要明确的研究(即，随机试验)来证明，与低LET质子治疗或先进的基于X射线的治疗(如调强放射治疗(IMRT)或立体定向身体放射治疗(SBRT))相比，高LET离子束放射治疗可带来更好的结果。北美粒子治疗联盟(NAPTA)汇集了辐射肿瘤学、医学和加速器物理、磁铁设计和放射生物学方面的专家，以及来自德国、意大利和日本现有离子束设施的国际顾问。NAPTA的主要目标是通过整合和发展所需的临床、生物和技术专业知识，在美国建立离子疗法的未来。在这个为期两年的初始资助期内，我们将：1)形成一个团队网络，对涉及PBRT的研发和临床研究有共同的愿景；2)通过开发基础设施，在所有合作机构共享的共同方案下治疗所有患者，从而加强临床PBRT研究；3)促进离子加速器、离子治疗的新的、低成本、紧凑/高效设计的开发。 (4)通过整合目前正在进行的项目和启动利用现有质子和离子设施的合作，促进发展与多项放射治疗有关的放射生物学方面的“新知识”。

 DESCRIPTION (provided by applicant): More than half of all cancer patients receive definitive radiotherapy (RT), usually with x-rays. Particle beam radiation therapy (PBRT) with low linear energy transfer (LET) protons is increasingly being used based on the assumption they can reduce complications and improve local control. High-LET PBRT, e.g., with carbon ions, may provide additional physical dose distribution advantages over low-LET RT. In addition, carbon and neon may yield an increased level of effectiveness against radioresistant and hypoxic (poorly oxygenated) tumor cells, which represent the most RT- and chemotherapy-resistant aggressive tumor cells. Adult patients with advanced tumors of the lung, head and neck, brain, esophagus, and pancreas may especially benefit from the advantages of high-LET ions, but the studies conducted to date have not been definitive. To justify the development of an expensive PBRT facility with high-LET ions, definitive studies (i.e., randomized trials) are needed to prove that high-LET ion beam RT results in improved outcomes compared to treatment with low- LET protons or advanced x-ray based therapy such as intensity modulated radiation (IMRT) or stereotactic body radiotherapy (SBRT). The North American Particle Therapy Alliance (NAPTA) brings together experts in radiation oncology, medical and accelerator physics, magnet design, and radiobiology with international consultants from the existing ion beam facilities in Germany, Italy, and Japan. The main objective of NAPTA is to build a future for ion therapy in the U.S. by integrating and developing the required clinical, biological and technical expertise. In this initil two-year funding period, we will: 1) form a network of teams with a common vision for R&D and clinical studies involving PBRT; 2) enhance clinical PBRT research by developing the infrastructure for treating all patients within common protocols shared by all partner institutions 3) facilitate the development of new, low-cost, compact/efficient designs for ion accelerators, ion gantries, treatment planning systems, and imaging technology; and 4) facilitate the development of "new knowledge" in radiobiology related to PBRT, by integration of currently ongoing projects and startup of collaborations with access to existing facilities with protons and ions.