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: 8795071
• 负责人: HAROLD M SWARTZ
• 金额: $ 155.18万
• 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/8795071
• 关键词: Address; Advanced Malignant Neoplasm; Adverse effects; Affect; Biocompatible; 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; Health; 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 measurement, partial pressure, arterial; Oxygen saturation measurement; Partial Pressure; Patients; Physicians; Process; Program Research Project Grants; Property; Protocols documentation; Radiation; Radiation Oncology; Radiation therapy; Radiation-Sensitizing Agents; Research; Site; Source; Staging; 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; cancer care; cancer cell; cancer therapy; chemotherapy; clinical application; clinical care; clinical practice; effective therapy; improved; in vivo; infrastructure development; instrument; lithium phthalocyanine; meetings; oncology program; particle; pre-clinical; preclinical evaluation; preclinical study; programs; radiation resistance; response; success; tool; treatment effect; treatment planning; tumor; tumor growth

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（由申请人提供）：尽管在全身治疗方面取得了进展，但氧仍然是所有放射致敏剂中最有效的，其敏感性增加了3倍。氧张力因个体、一天中的时间和所研究的器官而异。众所周知，许多自然过程（如肿瘤生长）和治疗过程会动态改变肿瘤中的pO2，并且同一类型肿瘤在同一阶段的个体中pO2是不同的。通过巧妙地、适应性地利用对肿瘤内氧张力的更好理解，潜在的收益是巨大的。目前尚无临床方法获得治疗条件下肿瘤pO2的准确、定量测量。本PPG提案的目的是改变这一现状，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。该方法基于EPR血氧测定法，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。该方法将能够个体化治疗，并验证旨在通过放射生物学显著量增加肿瘤中pO2的方法。PPG是三个机构的合作成果：达特茅斯学院是开发临床应用EPR血氧测定技术的基地，拥有开发体内EPR仪器和技术的广泛基础设施；布鲁塞尔大学和达特茅斯大学是临床前研究的重要来源证明了EPR血氧计的有效性；埃默里大学拥有领先的学术放射肿瘤学项目，并与达特茅斯大学合作使用体内EPR系统。PPG分为三个项目，每个项目涉及所有三个机构，并使用不同但互补的方法来推进临床EPR血氧测定。PPG的目标是证明一种可用于肿瘤pO2直接和重复测量的临床适用方法的能力已经实现，并且确实提供了使临床医生能够利用通过重复测量pO2获得的增强治疗机会所需的测量类型。它还将确定EPR定量测量肿瘤pO2与间接但目前更广泛用于推断肿瘤缺氧的临床方法之间的关系。PPG的成功将使未来的临床试验成为可能，从这些测量中获得的信息将用于改变治疗方法，并确定对结果的影响。