Ameliorating lymphocyte depletion and functional impairment following lung SBRT

改善肺 SBRT 后的淋巴细胞耗竭和功能损伤

• 批准号: 9805171
• 负责人: Krishni Wijesooriya
• 金额: $ 20.44万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9805171
• 关键词: Advanced Malignant Neoplasm; Algorithms; Antigens; Area; B-Lymphocytes; Benchmarking; Biological; Blood; Blood Volume; Brain Neoplasms; CD19 gene; CD3 Antigens; CD8-Positive T-Lymphocytes; CD8B1 gene; Cancer Patient; Cancer cell line; Chest; Clinical; Clinical Trials; Combined Modality Therapy; Complex; Complication; Coupling; Data; Data Set; Dependence; Development; Dose; Generations; Goals; Immune system; Immunity; Immunoglobulin G; Immunoglobulins; Immunosuppression; Immunotherapy; In Vitro; Influenza; Interferons; Lead; Literature; Lung; Lung Neoplasms; Lymph; Lymphocyte; Lymphocyte Count; Lymphocyte Depletion; Lymphocyte Function; Lymphopenia; Malignant neoplasm of lung; Mammary Neoplasms; Maps; Measurement; Methods; Modeling; NCAM1 gene; Normal tissue morphology; Organ; Output; Patient Care; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Pilot Projects; Pokeweed Mitogens; Population; Probability; Process; Protocols documentation; Publishing; Radiation; Radiation Dose Unit; Radiation Therapy Oncology Group; Radiation Tolerance; Radiation therapy; Randomized; Randomized Clinical Trials; Relapse; Research; Risk; Serum; Site; Structure; Survival Rate; System; T-Lymphocyte; Techniques; Testing; Tetanus Toxoid; Time; Tumor Volume; Tumor-infiltrating immune cells; Uterine Neoplasms; Validation; arm; body volume; dosimetry; functional disability; functional loss; immune function; improved; in vivo; pancreatic neoplasm; prediction algorithm; process optimization; prospective; prospective test; radiation delivery; radiation effect; response; side effect; simulation; standard of care; treatment planning; treatment strategy; trial comparing; tumor; tumor eradication

Abstract Objectives: To evaluate the efficacy of minimizing Stereotactic Body Radiation Therapy (SBRT) effects on lymphocytes and improving overall survival and immune function by selectively reducing dose to blood rich organs, and increasing the dose confomality in the thorax. Method: This will be achieved in two steps: (A) Determine lymphocyte depletion, phenotype and function of lymphocytes in optimized versus un-optimized plans in total of 50 patients under a randomized pilot study. We will evaluate peripheral blood mononuclear cells collected at baseline and at end of treatment, 4, and 24 weeks after lung SBRT on the clinical trial and compare the data for the two arms. (B) Improve the existing simulation algorithm to predict the total lymphocyte loss for a given Radiation Therapy (RT) beam plan using the clinical trial data. This model will take into account patient specific (i) total blood volume (ii) initial lymphocyte count (iii) tumor volume (iv) the organs from the Thorax CT data set (v) time dependent dose map through each organ for a given delivery system, and plan, and convolve these with general information from published literature such as (i) varying blood output to organs (ii) blood velocity for all organs (iii) Random mixing of blood after each trip through the exposed dose area, with the remaining blood volume of the body.

摘要 目的：评价最小化立体定向全身放射治疗(SBRT)的疗效。 选择性地塞米松对淋巴细胞的影响及提高总体存活率和免疫功能 减少对血液丰富器官的剂量，增加胸腔内的剂量配置。 方法：这将通过两个步骤来实现：(A)测定淋巴细胞耗竭、表型 优化方案与未优化方案下共50例患者的淋巴细胞功能 一项随机的初步研究。我们将评估在以下地点收集的外周血单核细胞 临床试验中的基线和治疗结束时，肺SBRT后4周和24周 比较两个手臂的数据。(B)改进现有的模拟算法，以预测 使用临床试验数据对给定的放射治疗(RT)射束计划的总淋巴细胞损失。 该模型将考虑患者的特异性(I)、总血容量(II)、初始淋巴细胞 计数(Iii)肿瘤体积(Iv)胸部CT数据集中的器官(V)时间依赖剂量 通过每个器官映射一个给定的递送系统，并计划，并将这些与一般 已发表文献中的信息，如(I)器官输血量的变化(Ii)血流速度 对于所有器官(III)每次通过暴露剂量区域后随机混合血液， 体内剩余的血量。