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（由申请人提供）：尽管全身治疗的进展，氧气仍然是所有辐射敏化剂中最有效的氧气，敏感性提高了3倍。氧气张力因个人，一天中的时间和器官的研究而变化。众所周知，许多天然（例如肿瘤生长）和治疗过程动态地改变了肿瘤中的PO2，并且在同一阶段，患有相同类型的肿瘤的个体中的PO2在不同。通过对肿瘤内氧气张力的改善理解的智能，适应性使用，潜在的增长是巨大的。当前，没有临床方法可以在治疗条件下对肿瘤PO2进行准确的定量测量。 PPG的这一建议的目的是改变这种情况，引入了一种实用有效的技术，为临床医生提供直接，可重复的，可重复的定量方法，以测量肿瘤和其他组织中的PO2。该方法基于EPR血氧饱和度，该法进行了广泛的临床前评估以及一组癌症患者的可行性测试。该方法将能够通过放射性生物学的大量量来个性化治疗和验证旨在增加肿瘤中PO2的方法。 PPG是三个机构的协作努力：达特茅斯（Dartmouth），它一直是开发临床适用的EPR血氧仪技术的站点，并且具有广泛的基础设施来开发体内EPR工具和技术；与达特茅斯（Dartmouth）一起的布鲁塞尔（Brussels）是许多关键临床前研究的非常重要的来源，证明了EPR血氧仪的有效性。和埃默里大学（Emory University）具有领先的学术放射肿瘤学计划，并且使用体内EPR系统与达特茅斯（Dartmouth）进行了以前的和持续的合作。 PPG在三个项目中组织，每个项目都涉及所有3个机构，并利用不同但免费的方法来推进临床EPR血氧仪。 PPG的目标是证明具有可用于直接和重复测量肿瘤PO2的临床适用方法的能力已实现，并且确实确实提供了使临床医生能够通过重复测量PO2获得增强的治疗机会所需的测量类型。它还将确定EPR对肿瘤PO2的定量测量与间接的肿瘤PO2之间的关系之间的关系，但目前广泛可用的临床方法用于推断肿瘤缺氧。该PPG的成功将使以后的临床试验成为可能，其中将这些测量的信息应用于更改治疗以及对结果的影响。