PROTON RADIATION THERAPY RESEARCH

目标和具体目标 癌症治疗的目标是治愈而不发病。放射治疗可能是一种有效的局部癌症治疗方法。虽然任何肿瘤都可以在足够的辐射下被杀死，但任何正常组织也可以在给定体积的足够剂量下受到伤害。挑战是只向那些含有肿瘤的组织提供适当的剂量。与可比的光子(X射线)场相比，没有超出目标的出射剂量的质子对正常组织的照射较少。这可以提高治愈率与并发症风险的治疗比率。 虽然许多患者已经在许多疾病部位接受了质子治疗，取得了令人印象深刻的临床结果，但我们相信，研究可以使质子在其他疾病部位得到应用并增强其应用。 这个多机构项目的目标是应用先进的质子放射计划和交付技术来改善非小细胞肺癌、肝癌、儿童髓母细胞瘤和横纹肌肉瘤、脊柱/颅底肉瘤和副鼻窦恶性肿瘤患者的预后。 我们假设，通过更好地利用和了解组织中的质子范围，以及研究和管理肿瘤和正常组织中的运动和解剖变化，我们可以提供更高精度的质子治疗，以进一步提高靶区覆盖和/或减少对附近关键结构的剂量。 为了验证这一假设，我们提出了四个综合项目：(1)质子剂量递增和质子与光子对照随机试验治疗非小细胞肺癌，(2)在具有挑战性的临床地点改善质子放射治疗的治疗比，(3)减少质子放射治疗的范围不确定性，(4)在质子放射治疗中实现所见即所得。质子物理相互作用足以实现更小的目标是：(1)了解安全裕度以及更稳健和更适形的剂量分布，使质子能够更接近其全部潜力，并验证这些优势是否能够可靠地实现；(2)在质子与光子治疗肺癌的随机临床试验中使用这些优势；以及(3)将这些优势用于一些肿瘤部位的质子治疗，这些部位被认为质子发挥着越来越重要的作用，而且过去被证明对临床医生有困难。

Objectives and Specific Aims The goal of cancer treatment is cure without morbidity. Radiation can be an effective locoregional cancer treatment. While any tumor can be killed with enough radiation, any normal tissue can also be injured with sufficient dose to a given volume. The challenge is to deliver the appropriate dose to only those tissues containing tumor. Protons, with no exit dose beyond the target, irradiate less normal tissue than comparable photon (X-ray) fields. This can improve the therapeutic ratio of cure probability to complication risk. While many patients have been treated with protons with impressive clinical results in a number of disease sites, we believe that research can enable and enhance the use of protons in other disease sites. The objective of this multi-institutional program project is to apply advanced proton radiation planning and delivery techniques to improve outcome for patients with non-small cell lung cancer, liver tumors, pediatric medulloblastoma and rhabdomyosarcoma, spine/skull base sarcomas, and paranasal sinus malignancies. We hypothesize that through better use and understanding of the proton range in tissue, and study and management of motion and anatomic changes in the tumor and normal tissues, we can deliver higher precision proton therapy to further improve target coverage and/or reduce dose to nearby critical structures. To test this hypothesis, we propose four integrated projects: (1) Proton Dose Escalation and Proton vs. Photon Randomized Trials for the Treatment of Nonsmall Cell Lung Cancer, (2)lmproving the Therapeutic Ration of Proton Radiation Therapy in Challenging Clinical Sites, (3) Reducing Range Uncertainties in Proton Radiation Therapy, (4) Achieving What-You-See-ls-What-You-Get in Proton Radiation Therapy. The proton physical interactions sufficient to allow smallerspecific aims are to (1) develop an understanding of safety margins as well as more robust and conformal dose distributions, allowing protons to more nearly meet their full potential, and to verify that these advantages can be reliably achieved; (2) use these advantages in randomized clinical trials of protons vs. photons in lung cancer; and (3) to use these advantages in the proton therapy of a number of tumor sites for which protons are judged to have an increasingly important role and which have proven problematic for clinicians in the past.