Proton Dose Escalation and Proton vs. Photon Randomized Trials

质子剂量递增和质子与光子随机试验

• 批准号: 8336785
• 负责人: Ritsuko Komaki
• 金额: $ 5.16万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8336785
• 关键词: Affect; Anatomy; Biological; Body Weight decreased; CCNE1 gene; Cancer Patient; Characteristics; Clinical; Clinical Trials; Common Terminology Criteria for Adverse Events; Complex; Conduct Clinical Trials; Development; Dose; Electromagnetic Energy; Enrollment; Evaluation; Foundations; Fractionation; Funding; Goals; Image; Institution; Investigation; Lead; Malignant neoplasm of lung; Maximum Tolerated Dose; Motion; Motivation; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Outcome; Patients; Phase; Phase I Clinical Trials; Photons; Physics; Pneumonia; Population; Positioning Attribute; Progression-Free Survivals; Protocols documentation; Proton Radiation; Protons; Quality of life; Radiation; Radiation therapy; Recurrence; Regimen; Research; Research Design; Research Methodology; Risk; Series; Solutions; Source; Staging; Structure; Structure of parenchyma of lung; Testing; Therapeutic Studies; Time; Tissues; Toxic effect; Treatment Efficacy; Tumor Volume; Uncertainty; anticancer research; cancer therapy; chemotherapy; density; follow-up; improved; lung volume; randomized trial; research and development; treatment planning; treatment site; treatment strategy; tumor

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.

项目1的总体目标是通过一系列非小细胞肺癌（NSCLC）临床研究确定 试验，无论是当前最先进的质子治疗还是通过物理学取得的进步 与光子疗法相比，项目 3 和 4 中提出的研究将带来更好的结果。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 由于分次内运动的挑战、分次间解剖学变化（例如，由于肿瘤 收缩和重量减轻）、内部不均匀性、肺组织密度低和其他来源 物理和生物的不确定性。这些因素影响质子的射程并导致剂量 治疗计划中看到的分布与患者实际接受的剂量分布不同 病人。初步试验将使用当前最先进的质子治疗技术进行。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。使用最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潜力。该项目的目标是： 1) II-IIIB 阶段 随机试验：可以实现在同等肿瘤控制的情况下降低肺炎发生率 在接受同步化疗的 II-IIIB 期 NSCLC 患者中使用质子与光子进行比较 并将在贝叶斯自适应随机试验中进行测试，2) II-IIIB 期 l/ll 剂量递增试验： 由于分数大小和总分数更高，II-IIIB 期患者的局部控制可以得到改善。 通过同时集成质子增强传递的总肿瘤体积的辐射剂量，而不增加 同步化疗时的毒性。 3) l/ll 期 l/ll 期试验：标准质子治疗 与传统疗法相比，分次治疗和更高的 BED 可能具有更高的最大耐受剂量 (MTD) 光子疗法，4) 阶段 //// 随机试验：质子疗法（来自目标 3）与最高剂量的比较 通过光子治疗安全实现的治疗方案可以改善中央 IA 期的局部控制 或 IB 期和选择性 II 期 (T3NOMO) NSCLC，5) 大分割（每分割 -10 CGE 或 更高）位于第一阶段中心的立体定向体质子治疗（SBPT）。其意义在于 我们的研究结果将使我们能够确定哪些非小细胞肺癌患者最有可能受益 质子治疗，并为合作试验奠定基础。