Proton Dose Escalation and Proton vs. Photon Randomized Trials

项目1的总体目标是通过一系列非小细胞肺癌(NSCLC)的临床 试验，无论是目前最先进的质子疗法还是通过物理学取得的进展 项目3和项目4中提出的研究将导致比光子治疗更好的结果。尽管 质子剂量分布的明显物理优势，这个问题的答案并不明显 由于部分内运动的挑战，部分间解剖变化(例如，由于肿瘤 收缩和体重减轻)、内部不均匀、肺组织低密度和其他来源 物理和生物上的不确定性。这些因素会影响质子的射程，并导致剂量 治疗计划上看到的分布与实际接受的剂量分布不同 有耐心的。初步试验将以目前最先进的质子疗法进行。物理学 项目3和项目4中提议的调查将导致提高质子剂量的准确性和质量 分配。利用先进的质子治疗技术进行的更多临床试验将 允许评估质子与光子的真实势能。本项目的目标是：1)第二阶段--IIIB 随机试验：在相当于肿瘤控制的情况下，肺炎发病率可能会降低 同时接受化疗的II-IIIB期非小细胞肺癌患者使用质子与光子的比较 并将在贝叶斯自适应随机试验中进行测试，2)第二阶段-第三阶段L/11剂量递增试验： II-IIIB期患者的局部控制可以得到改善，因为较高的部分大小和总 质子同时积分增强对肿瘤体积的辐射剂量不增加 同时使用化疗时的毒性。3)阶段L/11期L/11期试验：标准质子治疗 分级和更高的床层可能具有比传统的更高的最大耐受剂量(MTD) 光子治疗，4)阶段/随机试验：质子治疗(来自AIM 3)与最高剂量的比较 安全的光子治疗方案可以改善位于中心位置的IA期的局部控制 或IB阶段和选择性II阶段(T3NOMO)NSCLC，5)次分馏(每部分-10 CGE或 高等)立体定向体质子疗法(SBPT)的中心定位I期，其意义在于 我们的研究结果将使我们能够确定哪些NSCLC患者最有可能受益于 质子疗法，并为合作试验奠定基础。

The overall goal of Project 1 is to determine, through a series of non-small cell lung cancer (NSCLC) clinical trials, whether proton therapy in its current state of the art or with the advances achieved through physics research proposed in Projects 3 and 4 would lead to superior outcome compared to photon therapy. Despite the apparent physical advantages of proton dose distributions, the answer to this question is not obvious because of the challenges of intra-fractional motion, inter-fractional anatomic changes (e.g., due to tumor shrinkage and weight loss), internal inhomogeneities, low density of lung tissue and other sources of physical and biological uncertainties. These factors affect the range of protons and cause the dose distribution seen on a treatment plan to be different from the dose distribution actually received by the patient. Initial trials will be conducted with the current state of the art of proton therapy. Physics investigations proposed in Projects 3 and 4 will lead to improved accuracy and quality of proton dose distributions. Additional clinical trials conducted with the advanced state of the art of proton therapy will allow the evaluation of the true potential of protons vs. photons. The aims of this project are: 1) Stage II-IIIB Randomized Trial: a reduction in the rate of pneumonitis with equivalent tumor control may be realized using protons compared to photons in patients with stage II-IIIB NSCLC receiving concurrent chemotherapy and will be tested in a Bayesian adaptive randomized trial, 2) Stage II-IIIB Phase l/ll Dose Escalation Trial: local control can be improved in patients with stage II-IIIB as a result of higher fraction sizes and total radiation doses to gross tumor volume delivered by simultaneous integrated proton boosts without increasing toxicity when concurrent chemotherapy is used. 3) Stage l/ll Phase l/ll Trial: proton therapy with standard fractionation and higher BED may have a higher maximal tolerated dose (MTD) compared with conventional photon therapy, 4) Stage //// Randomized Trial: proton therapy (from Aim 3) compared to highest dose regimen safely achieved with photon therapy can lead to improved local control in centrally located stage IA or stage IB and selective stage II (T3NOMO) NSCLC, 5) Hypofractionated (-10 CGE per fraction or higher) Stereotactic Body Proton Therapy (SBPT) of centrally located Stage I. The significance is that the results of our studies will allow us to determine which NSCLC patients are most likely to benefit from proton therapy, and to set the stage for cooperative trials.