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）的临床研究， 试验，无论是质子治疗在其目前的艺术状态或通过物理学取得的进展， 项目3和4中提出的研究将导致优于光子治疗的结果。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 由于分次内运动的挑战，分次间的解剖变化（例如，由于肿瘤 收缩和重量损失）、内部不均匀性、肺组织低密度和其他来源的 物理和生物不确定性。这些因素影响质子的射程， 在治疗计划上看到的剂量分布与实际接受的剂量分布不同。 病人初步试验将采用质子治疗的最新技术水平进行。物理 项目3和4中提出的研究将提高质子剂量的准确性和质量 分布。使用先进的质子治疗技术进行的其他临床试验将 允许评估质子与光子的真实电势。该项目的目标是：1）第II-IIIB阶段 随机试验：可能实现肺炎发生率的降低和等效的肿瘤控制 在接受同步化疗的II-IIIB期NSCLC患者中使用质子与光子的比较 2）II-IIIB期I/II期剂量递增试验： II-IIIB期患者的局部控制可以得到改善，这是由于更高的分数大小和总的 通过同时整合的质子增强递送的总肿瘤体积的辐射剂量，而不增加 同时使用化疗时的毒性。3)I/II期I/II期试验：质子治疗与标准 分次和更高的BED可能具有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（目标3）与最高剂量的比较 光子治疗安全实现的方案可以改善中央定位IA期的局部控制 或IB期和选择性II期（T3 NOMO）NSCLC，5）高分级（~ 10 CGE/级分或 较高）中央定位I期立体定向体部质子治疗（SBPT）。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 质子治疗，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.