Krohn Kenneth A, Yeuh Bevan
Department of Radiology, University of Washington, Seattle, WA 98195-6004, USA.
Semin Oncol. 2008 Jun;35(3):262-73. doi: 10.1053/j.seminoncol.2008.03.001.
An inadequate supply of oxygen, hypoxia, is an important factor contributing to resistance to treatment in a number of tumor types, including head and neck cancer. Novel imaging methods have been applied to studies of this important prognostic factor. Mammalian cells need oxygen to live but O2 also participates in the cytotoxic effects of ionizing radiation. Hypoxia is often the result of abnormal blood vessels supplying the tumor, increased diffusion distances to tumor cells, and reduced O2 transport capacity of the blood. Its consequences are mediated by a series of hypoxia-initiated genomic changes activating angiogenesis, glycolysis, and other processes that enable tumor cells to survive or escape the O2-deficient environment. Hypoxia has been shown to be important in overall diminished therapeutic response, malignant progression, increased probability of recurrence, locoregional spread, and distant metastases. Strategies are being developed to surmount the cure-limiting consequences of hypoxia, but methods are needed to select patients most likely to benefit from these new treatments. Even though hypoxia is a common tumor phenotype, it is by no means universal and is often heterogeneous within an individual patient. This review considers the biology of hypoxia, its consequences with respect to treatment, methods for measuring oxygenation in tissues, modern techniques for imaging of regional hypoxia, and how information about the oxygenation status of tumors might impact treatment.
氧气供应不足,即缺氧,是导致包括头颈癌在内的多种肿瘤类型治疗抵抗的一个重要因素。新型成像方法已应用于对这一重要预后因素的研究。哺乳动物细胞需要氧气来维持生命,但氧气也参与电离辐射的细胞毒性作用。缺氧通常是肿瘤供血血管异常、肿瘤细胞扩散距离增加以及血液氧气运输能力降低的结果。其后果是由一系列缺氧引发的基因组变化介导的,这些变化激活血管生成、糖酵解和其他过程,使肿瘤细胞能够在缺氧环境中存活或逃脱。缺氧已被证明在总体治疗反应降低、恶性进展、复发概率增加、局部区域扩散和远处转移中起重要作用。正在开发克服缺氧导致的治愈限制后果的策略,但需要方法来选择最有可能从这些新治疗中受益的患者。尽管缺氧是一种常见的肿瘤表型,但它绝非普遍存在,而且在个体患者体内往往是异质性的。本综述探讨了缺氧的生物学特性、其对治疗的影响、组织氧合测量方法、区域缺氧成像的现代技术,以及肿瘤氧合状态信息如何影响治疗。