CLINICAL CORRELATIONS BETWEEN LATE NORMAL TISSUE END-POINTS AFTER RADIOTHERAPY - IMPLICATIONS FOR PREDICTIVE ASSAYS OF RADIOSENSITIVITY
CLINICAL CORRELATIONS BETWEEN LATE NORMAL TISSUE END-POINTS AFTER RADIOTHERAPY - IMPLICATIONS FOR PREDICTIVE ASSAYS OF RADIOSENSITIVITY
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DOI：
10.1016/0959-8049(93)90004-y
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发表时间：
1993-01-01
影响因子：
8.4
通讯作者：
OVERGAARD, J
中科院分区：
文献类型：
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作者：
BENTZEN, SM;OVERGAARD, M;OVERGAARD, J
某些遗传综合征与高细胞辐射敏感性相关的发现引起了人们的兴趣，人们对辐射敏感性的概念一般都应该有遗传成分。这激发了对用于预测细胞正常组织放射敏感性的测定的研究。如果这样的内在因素是晚期正常组织损伤发展的主要因素，那么这应该是可检测的，作为不同组织中发生损伤的概率之间的相关性。这一假设在一系列的229例乳腺切除术后放疗治疗的患者中进行了检验，并在治疗结束后16至71个月的一些晚期终点方面进行了评价。在每例患者中，在两个不同的治疗区域评价是否存在明显的皮下纤维化和毛细血管扩张：在5 mm蜡团下方的光子场中和用于治疗胸壁的电子场中。每部分使用两种不同的剂量，以及使用单一前光子场，并在腋窝中部水平规定剂量的事实，导致这些患者的总剂量和每部分剂量的实质性变化。放射敏感性的非组织特异性患者间差异将导致一个治疗区域中高于预期的反应与另一个区域中高于预期的反应相关。对于两个终点（毛细血管扩张或皮下纤维化）中的每一个，在一个治疗区域发生强于预期反应的患者在另一个区域也倾向于发生强于预期反应。因此，一个强大的主机因素似乎存在一个特定的端点。这是一个悬而未决的问题，这是否是由个体差异内在的放射敏感性，损伤的进展速度或其他解释。与此相反，当将两个晚期终点（纤维化和毛细血管扩张）配对时，未观察到显著相关性。因此，显示出比预期更强的纤维化的患者平均发展为显著的毛细血管扩张，其概率从其总剂量和每部分剂量中很好地预测。这些发现表明，晚期损伤的临床表达的测定必须对该类型的损伤具有特异性。
The discovery that certain genetic syndromes are associated with a high cellular radiosensitivity has stirred interest,in the concept that radiosensitivity of persons in general should have a genetic component. This has motivated research into assays for prediction of cellular normal tissue radiosensitivity. If such an intrinsic factor were a major factor in the development of late normal tissue injury, this should be detectable as a correlation between the probability of developing injury in different tissues. This hypothesis is tested in a series of 229 patients treated with postmastectomy radiotherapy and evaluated with respect to a number of late endpoints 16 to 71 months after the end of treatment. In each patient, the presence of marked subcutaneous fibrosis and telangiectasia were evaluated in two different treatment areas: in a photon field underneath a 5-mm wax bolus and in an abutted electron field used for treating the chest wall. The use of two different doses per fraction and the fact that a single anterior photon field was used with the dose prescribed at the level of the mid-axilla, led to a substantial variation in total dose and dose per fraction in these patients. A non-tissue-specific patient-to-patient difference in radiosensitivity would cause higher than expected reactions in one treatment area to be correlated with higher than expected reactions in the other area. For each of the two endpoints, telangiectasia or subcutaneous fibrosis, patients experiencing stronger than expected reactions in one treatment area tended to do so in the other area as well. Thus, a strong host factor appears to exist for a specific endpoint. It is an open question whether this is explained by individual variability in intrinsic radiosensitivity, progression rate of injury or other. Contrary to this, no significant correlation was seen when pairing the two late end-points, fibrosis and telangiectasia. Thus, patients showing stronger than expected fibrosis developed on average marked telangiectasia with a probability well predicted from their total dose and dose per fraction. These findings suggest that an assay for clinical expression of late injury would have to be specific for that type of injury.