PROTON RADIATION THERAPY RESEARCH

描述（由申请人提供）：目的和具体目标 任何肿瘤细胞都可以用足够高剂量的辐射根除;相反，任何正常组织都可以用足够剂量的辐射损伤到给定的体积。临床医生面临的挑战是仅向含有肿瘤的组织输送适当的剂量。质子辐射场没有超出目标的出口，与相当的光子（X射线）场相比，向正常组织输送的辐射较少。这提高了治疗率（治愈概率与并发症风险），因为正常组织的照射对患者没有益处。 我们在哈佛回旋加速器和弗朗西斯H. Burr质子治疗中心（FHBPTC）自1974年以来。我们在许多疾病部位的临床结局方面取得了显著进展，包括颅底和颈椎的软骨肉瘤和脊索瘤（分别为95%和50%的局部控制），鼻窦肿瘤（82%的局部控制），眼黑色素瘤（97%的局部控制）和前列腺癌（80%的生化无病）。在FHBPTC，我们已经能够扩大治疗的疾病范围，包括几乎任何解剖部位的儿科恶性肿瘤，包括麻醉下的颅脊髓轴治疗，鼻咽癌，呼吸门控下的肺和肝细胞肿瘤，以及骨盆和腹膜后肉瘤。 我们相信，在这一领域的研究可以进一步提高我们的质子束在临床上的利用，以提高治疗效果。我们假设，主要通过使用先进的成像技术，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。我们提出了3个综合项目（1）质子治疗的物理优势的临床应用，（2）优化质子在临床中的使用，（3）质子放射治疗的死亡率降低来验证这一假设。这些项目的具体目标是开发剂量引导质子治疗技术，包括PET/CT成像，以测量质子束对正电子发射体的激活，在器官运动的情况下控制范围，并推进强度调制质子治疗的束输送策略，以进一步提高治疗率。在选定的肿瘤紧密浸润正常组织的临床部位，还将探索靶向生物制剂的发病率降低。

DESCRIPTION (provided by applicant): Objectives and Specific Aims Any tumor cell can be eradicated with a sufficiently high dose of radiation; conversely, any normal tissue can be injured with sufficient dose to a given volume. The challenge for clinicians is to deliver the appropriate dose to only those tissues containing tumor. Proton radiation fields, with no exit beyond the target, deliver less radiation to normal tissues than comparable photon (x-ray) fields. This improves the therapeutic ratio (of cure probability to complication risk) because irradiation of normal tissue does not benefit the patient. We have treated nearly 7,000 cancer patients with proton therapy at the Harvard Cyclotron and Francis H. Burr Proton Therapy Center (FHBPTC) since 1974. We have achieved significant gains in clinical outcomes for a number of disease sites including chondrosarcomas and chordomas of the skull base and cervical spine (95% and 50% local control, respectively), paranasal sinus tumors (82% local control), ocular melanoma (97% local control), and prostate cancer (80% biochemically disease-free). At the FHBPTC, we have been able to expand the range of diseases treated to include pediatric malignancies at nearly any anatomic site including craniospinal axis treatment under anesthesia, nasopharyngeal carcinoma, lung and hepatocellular tumors under respiratory gating, and pelvic and retroperitoneal sarcomas. We believe that research in this field can further iimprove our utilization of the proton beam in the clinic to enhance treatment outcome. We hypothesize that, mainly through the use of advanced imaging technology, we can deliver higher precision proton therapy to further improve target coverage and/or reduced dose to nearby critical structures. We propose 3 integrated projects (1)Clinical Utilization of the Physical Advantages of Proton Therapy, (2)Optimizing the Use of Protons in the Clinic, and (3) Morbidity Reduction with Proton Radiation Therapy to test this hypothesis. The specific aims of the projects are to develop dose guided proton therapy techniques including PET/CT imaging to measure the activation of positron emitters through the proton beam, to control range in the presence of organ motion, and to advance beam delivery strategies for intensity modulated proton therapy to further improve therapeutic ratio. In selected clinical sites where tumor closely invests normal tissue, morbidity reduction with targetted biologic agents will also be explored.