Sindelar William F, Kinsella Timothy J
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Surg Oncol Clin N Am. 2003 Oct;12(4):925-42. doi: 10.1016/s1055-3207(03)00087-5.
Much experimental evidence has been accumulated assessing the tolerance of various tissues to IORT, and much of the tolerance data have resulted from the use of canine models. Guidelines of IORT tissue tolerance established in experimental models have been used in the clinical application of IORT at numerous institutions. Although the radiotolerance of differing tissues can vary among species, sufficient clinical experience has accumulated to validate the canine tissue tolerance model as representative of human tissue responses to IORT. Cellular effects from radiation principally stem from direct damage to DNA, and thus proliferating tissues are among the most radiosensitive, with arrested or abnormal cell division. These tissues can manifest striking early toxicity, reflecting the rate of cell division that is affected by the radiation. Irradiation of nonproliferating or slowly proliferating tissues may show little or no early toxicity, but late effects can be manifested to considerable and varying degrees. In much of this late toxicity, pathologic changes develop from progressive ischemia, brought about by the gradual obliteration of small blood vessels. Irradiated endothelium often becomes replaced by a thickened fibrous layer, which, in small vessels, leads to occlusion and ischemic necrotic changes in the supplied tissue. In larger vessels, fibrosis can lead to wall weakening and aneurysmal dilatation, rupture, or thrombosis. The common denominator, then, of radiation damage to many tissues is related to vascular effects. Although the tolerance to IORT-induced toxicity can vary considerably among tissues, doses ranging to 25 Gy can generally be tolerated without significant toxicity. Vital areas where IORT dose must be carefully monitored include critical vasculature, gastrointestinal viscera, ureter, significant motor or sensory nerve trunks, and central nervous system structures. Higher doses can generally be delivered safely to anatomic areas at risk for tumor that are at a distance from sensitive organs or tissues. The general principle providing the rationale of IORT should always be practiced: maximize the radiation dose to the tumor and tumor-harboring tissues while minimizing dose exposure to surrounding normal tissues.
已经积累了大量实验证据来评估各种组织对术中放疗（IORT）的耐受性，并且许多耐受性数据来自犬类模型的使用。在实验模型中建立的IORT组织耐受性指南已在众多机构的IORT临床应用中得到应用。尽管不同组织的放射耐受性在不同物种之间可能有所不同，但已经积累了足够的临床经验来验证犬类组织耐受性模型可代表人体组织对IORT的反应。辐射的细胞效应主要源于对DNA的直接损伤，因此增殖组织是最放射敏感的组织之一，会出现细胞分裂停滞或异常。这些组织可能表现出明显的早期毒性，反映了受辐射影响的细胞分裂速率。对非增殖或缓慢增殖组织的照射可能几乎没有或没有早期毒性，但后期效应可能会在相当程度上且以不同程度表现出来。在许多这种后期毒性中，病理变化是由小血管逐渐闭塞导致的进行性缺血发展而来的。受照射的内皮细胞常常被增厚的纤维层所取代，在小血管中，这会导致供应组织的闭塞和缺血性坏死变化。在较大血管中，纤维化可导致血管壁变薄和动脉瘤样扩张、破裂或血栓形成。那么，许多组织辐射损伤的共同特征与血管效应有关。尽管不同组织对IORT诱导毒性的耐受性差异很大，但一般可以耐受高达25 Gy的剂量而无明显毒性。必须仔细监测IORT剂量的重要区域包括关键血管、胃肠道脏器、输尿管、重要的运动或感觉神经干以及中枢神经系统结构。通常可以将更高剂量安全地施用于远离敏感器官或组织的有肿瘤风险的解剖区域。应始终遵循为IORT提供理论依据的一般原则：在使周围正常组织的剂量暴露最小化的同时，将肿瘤和容纳肿瘤的组织的辐射剂量最大化。
