Direct and Repeated Clinical Measurement of pO2 for Enhancing Cancer Therapy

直接和重复的 pO2 临床测量可增强癌症治疗

• 批准号: 9514093
• 负责人: Brian W. Pogue
• 金额: $ 137.3万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9514093
• 关键词: Address; Advanced Malignant Neoplasm; Adverse effects; Affect; Cancer Patient; Carbogen Breathing; Carbon; Caring; Cervix Uteri; Clinical; Clinical Medicine; Clinical Trials; Collaborations; Data; Development; Direct Repeats; Effectiveness; Electron Spin Resonance Spectroscopy; Ensure; Fibrosis; Future; Goals; Head and Neck Cancer; Human; Hyperbaric Oxygenation; Hypoxia; India ink stain; Individual; Institution; Intervention; Measurement; Measures; Methodology; Methods; Monitor; Normal tissue morphology; Operative Surgical Procedures; Organ; Outcome; Oxygen; Oxygen saturation measurement; Partial Pressure; Patients; Physicians; Process; Program Research Project Grants; Property; Protocols documentation; Radiation; Radiation Oncology; Radiation induced damage; Radiation therapy; Radiation-Sensitizing Agents; Research; Selection for Treatments; Site; Source; System; Systemic Therapy; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Treatment Efficacy; Tumor Oxygenation; United States National Institutes of Health; Universities; antiangiogenesis therapy; base; biomaterial compatibility; cancer care; cancer cell; cancer therapy; chemotherapy; clinical application; clinical care; clinical practice; effective therapy; improved; in vivo; individualized medicine; infrastructure development; instrument; lithium phthalocyanine; oncology program; particle; pre-clinical; preclinical evaluation; preclinical study; programs; public health relevance; radiation effect; radiation resistance; response; success; targeted agent; tool; treatment effect; treatment optimization; treatment planning; tumor; tumor growth; tumor hypoxia; virtual

DESCRIPTION (provided by applicant): Despite advances in systemic therapy, oxygen remains the most potent of all radiation sensitizers, increasing sensitivity by a factor of 3. Oxygen tension varies by individual, by time of day, and by organ being studied. It also is well known that many of the natural (e.g. tumor growth) and therapeutic processes change the pO2 in tumors dynamically and that pO2 in tumors varies among individuals with the same type of tumor in the same stage. The potential gains by making smart, adaptive use of an improved understanding of the oxygen tension within a tumor are enormous. Currently there are no clinical methods to obtain accurate, quantitative measurements of tumor pO2 under treatment conditions. The purpose of this proposal for a PPG is to change this situation, introducing a practical and effective technology to provide a direct, repeatable, quantitative method for clinicians to measure pO2 in tumors and in other tissues. This method is based on EPR oximetry, which has undergone extensive preclinical evaluation as well as feasibility testing in a small set of cancer patients. This method will be able to individualize therapy and validate methods aimed at increasing the pO2 in tumors by radiobiologically significant amounts. The PPG is a collaborative effort of three institutions: Dartmouth which has been the site that has developed clinically applicable EPR oximetry techniques and which has an extensive infrastructure for the development of in vivo EPR instruments and techniques; Brussels which has together with Dartmouth been a very significant source of many of the key preclinical studies demonstrating the effectiveness of EPR oximetry; and Emory University which has a leading academic Radiation Oncology program and has previous and ongoing collaboration with Dartmouth using in vivo EPR system. The PPG is organized in three projects, with each project involving all 3 institutions and utilizing different but complimentary approaches to advance clinical EPR oximetry. The goals of the PPG are to demonstrate that the capability of having a clinically applicable method available for direct and repeated measurements of tumor pO2 has been realized and does indeed provide the types of measurements required to enable clinicians to exploit the enhanced therapeutic opportunities that can be obtained by repeated measurements of pO2. It also will determine the relationships between the quantitative measurements of tumor pO2 by EPR with the indirect but currently more widely available clinical methods used to infer to tumor hypoxia. The success of this PPG will make future clinical trials possible where the information from these measurements is applied to change treatment and the effects on outcomes determined.

描述(申请人提供)：尽管全身治疗取得了进展，氧气仍然是所有辐射敏感剂中最有效的，使敏感度增加了3倍。氧分压因个体、一天中的时间和正在研究的器官而异。众所周知，许多自然过程(如肿瘤生长)和治疗过程都会动态改变肿瘤中的PO2，同一肿瘤类型在同一阶段的个体之间肿瘤中的PO2也不同。通过智能地、适应性地使用对肿瘤内氧气张力的更好的理解，潜在的收益是巨大的。目前还没有临床方法可以在治疗条件下准确、定量地测量肿瘤的氧分压。这项针对PPG的建议旨在改变这种情况，引入一种实用有效的技术，为临床医生提供一种直接、可重复、定量的方法来测量肿瘤和其他组织中的PO2。这种方法是基于EPR血氧测定法，它已经在一小部分癌症患者中进行了广泛的临床前评估和可行性测试。这种方法将能够个体化治疗，并验证旨在通过放射生物学显著增加肿瘤中PO2的方法。PPG是三个机构共同努力的成果：达特茅斯大学已经开发了临床适用的EPR血氧仪技术，并为体内EPR仪器和技术的开发提供了广泛的基础设施；布鲁塞尔与达特茅斯大学一起成为许多证明EPR血氧仪有效性的关键临床前研究的重要来源；以及埃默里大学，它拥有领先的学术放射肿瘤学项目，并一直在使用体内EPR系统与达特茅斯大学进行合作。PPG由三个项目组成，每个项目涉及所有三个机构，并利用不同但互补的方法来推进临床EPR血氧测定。PPG的目标是证明已经实现了临床上可用于直接和重复测量肿瘤PO2的方法的能力，并且确实提供了使临床医生能够利用通过重复测量PO2可以获得的增强治疗机会所需的测量类型。它还将确定EPR对肿瘤PO2的定量测量与目前更广泛使用的间接临床方法之间的关系，这些方法用于推断肿瘤缺氧。PPG的成功将使未来的临床试验成为可能，在这些试验中，来自这些测量的信息将被应用于改变治疗方法，并对确定的结果产生影响。