Dose painting based on hypoxia and proliferative response

基于缺氧和增殖反应的剂量绘制

• 批准号: 7741423
• 负责人: ROBERT JERAJ
• 金额: $ 29.85万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7741423
• 关键词: Adverse effects; Aftercare; Biologic Characteristic; Biological; Biopsy Specimen; Canis familiaris; Cell Proliferation; Clinical; Development; Disease-Free Survival; Dose; Ensure; Funding; Human; Hypoxia; Image; Individual; Intensity-Modulated Radiotherapy; Investigation; Metabolism; Modeling; Nose; Outcome; PET/CT scan; Patients; Phenotype; Positioning Attribute; Positron-Emission Tomography; Property; Radiation; Radiation therapy; Recurrence; Scanning; Spatial Distribution; Survival Rate; Testing; Therapeutic; Tissues; Translations; Tumor-Associated Process; base; cancer therapy; experience; fluorodeoxyglucose positron emission tomography; improved; in vivo; molecular imaging; population based; public health relevance; response; tool; treatment response; tumor

DESCRIPTION (provided by applicant): The next significant advance in cancer therapy will occur with the paradigm shift from a population-based to a personalized patient-based dose prescription. In radiation therapy this paradigm shift will require, not only adjustment of the total dose prescribed, but also a shift from the current standard of uniform dose prescription to a non-uniform dose prescription, which will be tailored to the spatial distribution of biological properties in the tumor - the process most often termed "dose-painting". To ensure safe translation to human patients, we propose a thorough investigation on a canine spontaneous nasal tumor model. Four treatment groups will be considered: (1) Standard radiotherapy, (2) Uniform dose escalation, (3) Non- uniform dose escalation based on hypoxia and (4) Non-uniform dose escalation based on proliferative response. PET/CT imaging will be performed to guide treatment dose prescription and evaluate treatment response. FLT-PET will be used as a surrogate of cell proliferation, CuATSM-PET as a surrogate of tumor hypoxia and FDG-PET as a surrogate of tumor metabolism. Correlation to biological surrogates will be established by performing extensive IHC assessment on a tissue biopsy sample taken prior to the start of radiation therapy. The overall hypothesis is that non-uniform dose escalation based on biological imaging (dose painting) leads to more effective radiotherapy than uniform dose escalation delivering the same integral dose boost. This hypothesis will be tested within three specific aims: Specific Aim 1: To compare uniform dose escalation to standard therapy Specific Aim 2: To compare non-uniform dose escalation based on hypoxia (hypoxia-based dose painting) to uniform dose escalation Specific Aim 3: To compare non-uniform dose escalation based on proliferative response (proliferative response-based dose painting) to uniform dose escalation In addition, we will perform three auxiliary studies: Auxiliary Study 1: To correlate early proliferative response and pre-treatment hypoxia to treatment response Auxiliary Study 2: To correlate early proliferative response to reoxygenation. Auxiliary Study 3: To spatially correlate early proliferative response to the position o tumor recurrence. PUBLIC HEALTH RELEVANCE: Individualized radiotherapy, where radiation dose will be tailored to individual patient tumor biological characteristics, is the next logical step in radiotherapy development. This approach will revolutionize the way that radiotherapy is prescribed and planned, and will improve the therapeutic outcome in terms of local tumor control and side-effects to unaffected tissue.

描述（由申请人提供）： 癌症治疗的下一个重大进展将随着从基于人群的个性化剂量处方的范式转移。在放射疗法中，这种范式转移不仅需要调整总剂量的总剂量，而且还需要从当前均匀剂量处方的标准到非均匀剂量处方的转变，该剂量处方将定制为肿瘤中生物学特性的空间分布 - 该过程最常被称为“剂量滴剂”。为了确保对人类患者的安全翻译，我们建议对犬自发鼻肿瘤模型进行彻底研究。将考虑四个治疗组：（1）标准放疗，（2）基于缺氧的剂量升级，（3）基于缺氧的非均匀剂量升级，以及（4）基于增殖反应的不均匀剂量升级。将进行PET/CT成像以指导治疗剂量处方并评估治疗反应。 FLT-PET将用作细胞增殖的替代物，Cuatsm-Pet作为肿瘤缺氧的替代物和FDG-PET作为肿瘤代谢的替代物。通过对放射治疗开始之前对组织活检样本进行广泛的IHC评估，将建立与生物替代物的相关性。总体假设是，基于生物成像（剂量绘画）的非均匀剂量升级会导致比均匀剂量升级更有效的放射疗法，从而提供相同的整体剂量增强。该假设将在三个具体目标中进行检验：具体目的1：比较均匀的剂量升级与标准治疗的特定目的2：比较基于缺氧（基于低氧剂量的剂量绘画）的非均匀剂量升级与均匀剂量升级与特定剂量升级的目的3：基于剂量升级的剂量反应（替代剂量升剂）的替代剂量升高（替代剂量升高）（在均匀的剂量升级方面）的均匀剂量升高（替代剂量升高）（替代剂量升高）（替代剂量升高）（替代剂量升高）（替代）的剂量升高（三项辅助研究：辅助研究1：将早期增殖反应和治疗前的缺氧与治疗反应辅助研究相关联2：将早期增生响应与重氧的早期增殖反应相关。辅助研究3：要在空间上与肿瘤复发位置的早期增殖反应相关。公共卫生相关性：个性化放射疗法，将针对个体患者肿瘤生物学特征量身定制放射剂量，这是放射治疗开发的下一个逻辑步骤。这种方法将彻底改变放射疗法的处方和计划的方式，并将在局部肿瘤控制和对未受影响的组织的副作用方面改善治疗结果。