Turesson I, Notter G
Int J Radiat Oncol Biol Phys. 1986 Apr;12(4):603-9. doi: 10.1016/0360-3016(86)90069-6.
Alterations in the microcirculation and parenchymal cell loss are common phenomena after irradiation of different organs. Whether parenchymal cell loss is a process well dissociated from vasculoconnective damage, or a consequence of this, is much debated. However, comprehensive radiopathological studies have shown that vasculoconnective tissue is an important common target for late effects in various organs. Scoring of skin telangiectasia was used by us as a clinical assay of late tissue effects after different dose schedules. All studies were done prospectively with standardized skin area, field size and radiation quality. The patients were scored regularly up to 10 years. The number of patients at risk for a prescribed score versus time was calculated with the life-table method. The late effects after 5 X 2.0 Gy/wk, in the dose range 40 to 70 Gy and after 2 X 4.0 Gy/wk, in the dose range 40 to 56 Gy have been established. The skin dose is 90% of the referred dose. Dose-response curves, relating the proportion of patients with a certain score at a fixed time and radiation dose and dose-latency curves, relating the latent period for a fixed proportion of patients with a certain score and radiation dose, were constructed. The analysis shows that: ED10/5 yr and ED50/5 yr for 5 X 2.0 Gy/wk is 50 Gy and 65 Gy, respectively, for distinct telangiectasia; The latent period, concerning both a certain frequency and degree of reaction, varies exponentially with dose level; The latent period for 50% of the patients, to obtain a certain score, LP50, is correlated to that for 10%, LP10, with LP50/LP10 = 2.2 +/- 0.2 (S.D.). This correlation is independent of score, total dose, and fractionation; Isoeffective doses for 5 X 2.0 Gy/wk and 2 X 4.0 Gy/wk, determined from the dose-response curves, resulted in the repair exp N between 0.31 and 0.32 and alpha/beta ratio between 2.9 and 3.1 Gy and determined from the dose-latency curves in exp N between 0.30 and 0.32 and alpha/beta ratio between 3.4 and 2.9 Gy. In conclusion, frequent and careful follow-up with registration of normal tissue reactions, until at least 10% of the patients have obtained the prescribed effect, is predictive for the further progression of the late effects. The fractionation characteristics for telangiectasia agree well with those for animal experimental morphological and functional endpoints for late effects in different organs and support the relevance of telangiectasia as a model for predicting late effects.
不同器官受照射后，微循环改变和实质细胞丢失是常见现象。实质细胞丢失是一个与血管结缔组织损伤完全分离的过程，还是其结果，这一问题备受争议。然而，全面的放射病理学研究表明，血管结缔组织是各器官晚期效应的一个重要共同靶点。我们采用皮肤毛细血管扩张评分作为不同剂量方案后晚期组织效应的临床检测方法。所有研究均以前瞻性方式进行，皮肤面积、照射野大小和辐射质量均标准化。对患者进行定期评分，最长至10年。采用寿命表法计算达到规定评分的风险患者数量与时间的关系。已确定了每周5次、每次2.0 Gy，剂量范围为40至70 Gy，以及每周2次、每次4.0 Gy，剂量范围为40至56 Gy照射后的晚期效应。皮肤剂量为参考剂量的90%。构建了剂量反应曲线，即固定时间和辐射剂量下具有特定评分的患者比例与剂量的关系曲线，以及剂量潜伏期曲线，即具有特定评分和辐射剂量的固定比例患者的潜伏期与剂量的关系曲线。分析表明：每周5次、每次2.0 Gy照射时，明显毛细血管扩张的5年ED10和5年ED50分别为50 Gy和65 Gy；特定频率和反应程度的潜伏期随剂量水平呈指数变化；50%患者达到特定评分的潜伏期LP50与10%患者的潜伏期LP10相关，LP50/LP10 = 2.2 +/- 0.2（标准差）。这种相关性与评分、总剂量和分割方式无关；根据剂量反应曲线确定的每周5次、每次2.0 Gy和每周2次、每次4.0 Gy的等效剂量，修复指数N在0.31至0.32之间，α/β比值在2.9至3.1 Gy之间，根据剂量潜伏期曲线确定的修复指数N在0.30至0.32之间，α/β比值在3.4至2.9 Gy之间。总之，进行频繁且仔细的随访，记录正常组织反应，直至至少10%的患者出现规定效应，可预测晚期效应的进一步发展。毛细血管扩张的分割特征与不同器官晚期效应的动物实验形态学和功能终点的特征非常吻合，支持将毛细血管扩张作为预测晚期效应模型的相关性。
