EXPERIMENTAL INTRAOPERATIVE RADIOTHERAPY

描述：（改编自研究者摘要）长期

DESCRIPTION: (Adapted from investigator's abstract) The long term objective of this research is to provide information on the type and expected frequency of injury to normal periaortic tissues following intraoperative irradiation (IORT). There is great interest in IORT for improving control of tumors located near radiosensitive structures or involving large vessels or nerves. A specific aim of this study is to determine the effect of the volume of normal tissue irradiated. As the major advantage of IORT is to restrict the irradiated volume as much as possible, information concerning dose volume relationships is most important. Another objective of the volume study is to determine the progression and pathogenesis of slowly developing lesions in canine periaortic tissues at variable intervals following IORT. This will be done primarily with specialized histologic techniques including ultrastructural studies. Of particular interest is the cellular response near the periphery of the irradiated field as migration from non-irradiated tissue may modify the tissue response depending on volume irradiated. A second aim of this is to estimate the amount and rate of repair of periaortic tissues using split dose techniques with variable intervals between the first and second dose. Sequential functional examinations will include aortagrams and aortic pressure measurements, observations for peripheral nerve injury, electrophysiologic measurements, intravenous urography, and blood and urine chemistries. Other functional examinations include ureteral electromyography and pressure measurements. Necropsies of dogs three years following treatment will provide tissues for morphometric analysis of the aorta, arteries, microvasculature, peripheral nerves, muscles, ureters, and lumbar vertebrae. Of special interest will be the percentage volume changes in parenchyma, stroma and microvasculature. Development of thrombi and aneurysms in vessels, neuropathies, structures of ureters and bone necrosis will be evaluated. This information will provide guidance to those using IORT so that the risk of late developing serious normal tissue complications can be reduced. The questions asked are of more general interest in radiation therapy than just for intraoperative radiation therapy. The tissues evaluated are the entire vascular tree from aorta to capillaries, peripheral nerves, muscle, bone and ureters. There is little research specifically directed at those tissues even though they include the most common tissues at risk in radiation therapy and in many cases are dose limiting. Because of the size of the dog, they can all be studied in the same animal and the same field of irradiation. Questions concerning radiation repair by these late responding tissues and volume effects have not been answered and are of major concern in radiation therapy. Another important attribute of the animal model proposed is that functional and histologic studies can be done on the same animal. The functional studies are clinically relevant, the end points of paralysis, ureteral structure, aneurysm, thrombosis, bone necrosis and muscle atrophy are obviously important clinical consequences of radiation. Careful histologic evaluations permit dose response comparisons and insight into the basic mechanisms and cellular interactions leading to late consequences of irradiation.