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。放射治疗是一种有效的局部癌症治疗方法。虽然任何肿瘤都可以用足够的辐射杀死，但任何正常组织也可以用足够的剂量损伤到给定的体积。挑战在于仅向含有肿瘤的组织递送适当的剂量。质子，没有超出目标的出口剂量，比可比的光子（X射线）场照射更少的正常组织。这可以提高治愈概率与并发症风险的治疗比。 虽然许多患者在许多疾病部位接受了质子治疗，并取得了令人印象深刻的临床效果，但我们相信，研究可以使质子在其他疾病部位的使用成为可能并得到加强。 该多机构计划项目的目的是应用先进的质子放射计划和输送技术，以改善非小细胞肺癌、肝脏肿瘤、小儿髓母细胞瘤和横纹肌肉瘤、脊柱/颅底肉瘤和鼻窦恶性肿瘤患者的结局。 我们假设，通过更好地使用和理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学变化，我们可以提供更高精度的质子治疗，以进一步提高目标覆盖率和/或减少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治疗非小细胞肺癌的随机试验，（2）提高质子放射治疗在临床场所的治疗比，（3）减少质子放射治疗的范围不确定性，（4）实现质子放射治疗的所见即所得。质子物理相互作用足以实现更小的特定目标是：（1）了解安全裕度以及更稳健和适形的剂量分布，使质子更接近其全部潜力，并验证这些优势可以可靠地实现;（2）在肺癌中质子与光子的随机临床试验中使用这些优势;以及（3）在质子治疗许多肿瘤部位中使用这些优点，对于这些肿瘤部位，质子被判断为具有越来越重要的作用，并且过去已经证明对于临床医生是有问题的。

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.