Oxygen Guided Hypofractionated Radiotherapy for Gliomas

氧引导胶质瘤大分割放射治疗

• 批准号: 7425400
• 负责人: NADEEM KHAN
• 金额: $ 27.56万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7425400
• 关键词: Address; Adjuvant; Affect; Animals; Apoptosis; Blood flow; Brain; Brain Neoplasms; Brain Part; Carbogen; Cells; Cerebrum; Characteristics; Clinical; Condition; Contralateral; Data; Dependence; Development; Dose; Effectiveness; Electron Spin Resonance Spectroscopy; Fractionation; Genetic; Glioblastoma; Glioma; Goals; Histology; Hyperbaric Oxygen; Hyperbaric Oxygenation; Hypoxia; Individual; Induction of Apoptosis; Intervention; Intracranial Neoplasms; Invasive; Knowledge; Magnetic Resonance Imaging; Malignant Glioma; Malignant Neoplasms; Measurement; Measures; Methodology; Methods; Modality; Molecular; Neuraxis; Operative Surgical Procedures; Outcome; Oxygen; Oxygen saturation measurement; Partial Pressure; Patients; Physiological; Physiology; Postoperative Period; Principal Investigator; Radiation; Radiation therapy; Radiation-Induced Change; Relative (related person); Research Personnel; Scheme; Site; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Treatment Effectiveness; Treatment Protocols; Tumor Oxygenation; Tumor Tissue; Tumor Volume; Variant; Week; base; blood perfusion; improved; in vivo; irradiation; novel; novel strategies; outcome forecast; prognostic; programs; response; success; treatment planning; tumor; tumor growth

DESCRIPTION (provided by applicant): The prognosis for patients with malignant gliomas remains dismal in spite of many advances in surgical, chemotherapeutic and radiotherapeutic modalities. Treatment options are determined mostly empirically, and therefore new approaches based on tumor physiology or genetics are needed to improve outcome for patients with this highly malignant tumor. Brain tumors are treated with a spectrum of fractionation regimens based on the clinical and anatomical characteristics of the tumor but are rarely based on the molecular or physiological characteristics of the individual tumor. Hypoxia is a known factor in radioresistance. Radiotherapy is expected to change oxygenation in tumors, this effect is likely to vary with the dose per fraction and interval between doses, and therefore may significantly alter the effectiveness of the treatment. Establishing the presence of hypoxia and particularly the possibility of exploiting post-irradiation reoxygenation in gliomas offers the promise of developing individualized RT regimens that might improve the response of radioresistant glioma cells to therapy. We hypothesize that the therapeutic outcome of hypofractionated radiotherapy of gliomas can be significantly enhanced if radiotherapy is used at times of optimal tumor oxygenation and the use of hyperoxic therapies in conjunction with hypofractionated radiotherapy can 'be optimized by the use of information on oxygen levels in the tumors. This would be a highly significant development for gliomas due to their poor radiotherapy prognosis. We will measure partial pressure of oxygen (pO2) using multi-site EPR (Electron Paramagnetic Resonance) oximetry in experimental intracranial 9L tumors undergoing hypofractionated radiotherapy and relate hypoxia and changes in hypoxia to outcome in terms of tumor growth delay. This has not been possible previously due to a lack of suitable in vivo techniques for repeated non-invasive pO2 measurements in the same tumor during the entire course of therapy. MRI and histology will be used to determine tumor tissue characteristics that may be related to the mechanism of the changes in oxygen, at time points during therapy and in relation to measured tumor pO2. We also will determine the relationship between radiation-induced changes in tumor oxygenation and the extent of tumor pO2 increases during hyperoxygenation with hyperbaric oxygen therapy (100% oxygen at 2-4 ATA) and carbogen (95%O2/5%CO2). This study will provide a rationale basis for the application of hypofractionated stereotactic radiotherapy so that it can be used with optimal effectiveness, and establish methodology that can be used to enhanced therapeutic outcome of gliomas in particular but also for tumors in general.

描述（由申请人提供）：尽管手术，化学治疗和放射治疗方法取得了许多进步，但针对恶性神经胶质瘤患者的预后仍然令人沮丧。治疗选择主要是在经验上确定的，因此需要基于肿瘤生理或遗传学的新方法来改善这种高度恶性肿瘤的患者的预后。根据肿瘤的临床和解剖学特征，用一系列分馏方案处理脑肿瘤，但很少基于单个肿瘤的分子或生理特征。缺氧是辐射抗性的已知因素。预计放射疗法会改变肿瘤中的氧合作用，这种作用可能随着剂量的剂量和剂量间隔的剂量而变化，因此可能会显着改变治疗的有效性。建立缺氧的存在，尤其是在神经胶质瘤中利用辐照后重氧的可能性，这有望开发个性化的RT方案，从而可以改善辐射耐胶质瘤细胞对治疗的反应。我们假设，如果在最佳肿瘤氧合时使用放射疗法，并且可以通过在thumors中使用氧气水平的信息来优化，则可以显着增强神经胶质瘤放射疗法的治疗结果。由于胶质瘤的放射疗法不良，这对于胶质瘤而言将是一个非常重要的发展。我们将使用多站点EPR（电子顺磁共振）的氧气（PO2）在实验性颅内9L肿瘤中进行氧气（PO2）的副压，并在肿瘤生长延迟方面与缺氧和缺氧的变化相关联和缺氧与预后的变化相关。由于缺乏适合在整个治疗过程中相同肿瘤中反复的非侵入性PO2测量的体内技术，因此这是不可能的。 MRI和组织学将用于确定可能与氧气变化，治疗过程中的时间点以及与测量的肿瘤PO2有关的机理有关的肿瘤组织特征。我们还将确定辐射诱导的肿瘤氧合变化与肿瘤PO2在高氧中使用高氧疗法（2-4 ATA时100％氧）和碳原（95％O2/5％CO2）的关系之间的关系。这项研究将为应用降量的立体定向放射疗法提供理由基础，以便可以以最佳有效性使用，并建立可用于增强神经胶质瘤的治疗结果的方法，尤其是肿瘤。