Oxygen Guided Hypofractionated Radiotherapy for Gliomas

氧引导胶质瘤大分割放射治疗

• 批准号: 7925726
• 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 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925726
• 关键词: Address; Adjuvant; Affect; Animals; Apoptosis; Blood flow; Brain; Brain Neoplasms; Brain Part; Carbogen; Cells; Cerebrum; Characteristics; Clinical; 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; 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; Regimen; Relative (related person); Research Personnel; Scheme; Site; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Treatment Effectiveness; Tumor Oxygenation; Tumor Tissue; Tumor Volume; Variant; base; blood perfusion; conventional therapy; improved; in vivo; irradiation; novel; novel strategies; outcome forecast; prognostic indicator; 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）：尽管在手术、化疗和放疗方式上取得了许多进展，但恶性胶质瘤患者的预后仍然很差。治疗方案大多是凭经验确定的，因此需要基于肿瘤生理学或遗传学的新方法来改善这种高度恶性肿瘤患者的预后。根据肿瘤的临床和解剖学特征，采用一系列分级方案治疗脑肿瘤，但很少基于个体肿瘤的分子或生理学特征。缺氧是辐射抗性的已知因素。放射治疗预期会改变肿瘤中的氧合，这种作用可能会随着每次剂量和剂量间隔而变化，因此可能会显著改变治疗的有效性。建立缺氧的存在，特别是利用放射后再氧合的可能性，在胶质瘤提供了发展个性化的RT方案，可能会提高放射抗性胶质瘤细胞的治疗反应的承诺。我们假设，如果在最佳肿瘤氧合时间使用放射治疗，则胶质瘤的大分割放射治疗的治疗结果可以显著增强，并且高氧治疗与大分割放射治疗结合使用可以通过使用肿瘤中氧水平的信息来优化。由于胶质瘤的放疗预后较差，这对于胶质瘤来说将是一个非常重要的发展。我们将使用多部位EPR（电子顺磁共振）血氧饱和度测定法测量接受大分割放射治疗的实验性颅内9 L肿瘤的氧分压（pO 2），并将缺氧和缺氧变化与肿瘤生长延迟方面的结果联系起来。由于缺乏合适的体内技术，在整个治疗过程中，在同一肿瘤中重复进行非侵入性pO 2测量，这在以前是不可能的。MRI和组织学将用于确定可能与氧变化机制相关的肿瘤组织特征，在治疗期间的时间点以及与测量的肿瘤pO 2相关。我们还将确定放射诱导的肿瘤氧合变化与高压氧治疗（100%氧气，2-4 ATA）和Carbogen（95%O2/5%CO2）高氧期间肿瘤pO 2升高程度之间的关系。本研究将为应用大分割立体定向放射治疗提供理论基础，使其能够以最佳效果使用，并建立可用于提高胶质瘤治疗效果的方法，但也适用于一般肿瘤。

项目成果

Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator-based oximetry.

• DOI: 10.1002/ijc.29132
• 发表时间: 2015-04-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Hou, Huagang;Nemani, Venkata Krishnamurthy;Du, Gaixin;Montano, Ryan;Song, Rui;Gimi, Barjor;Swartz, Harold M.;Eastman, Alan;Khan, Nadeem
• 通讯作者: Khan, Nadeem

Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.

• DOI: 10.1016/j.jneumeth.2011.10.026
• 发表时间: 2012-02-15
• 期刊: JOURNAL OF NEUROSCIENCE METHODS
• 影响因子: 3
• 作者: Khan, Nadeem;Mupparaju, Sriram;Hou, Huagang;Williams, Benjamin B.;Swartz, Harold
• 通讯作者: Swartz, Harold

Assessment of the changes in 9L and C6 glioma pO2 by EPR oximetry as a prognostic indicator of differential response to radiotherapy.

• DOI: 10.1667/rr2811.1
• 发表时间: 2013-03
• 期刊: Radiation research
• 影响因子: 3.4
• 作者: Hou H;Mupparaju SP;Lariviere JP;Hodge S;Gui J;Swartz HM;Khan N
• 通讯作者: Khan N