Peschke P, Hahn E W, Wolber G, Hildenbrand D, Zuna I
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Radiologie, Heidelberg, Germany.
Int J Radiat Biol. 1996 Nov;70(5):609-16. doi: 10.1080/095530096144824.
To determine the most effective means by which to apply the combined treatments of local tumour hyperthermia (LTH) with interstitial low dose-rate irradiation (IRT) we examined the significance of such factors as dose-rate of radiation, and the sequence and frequency of hyperthermia applications in the anaplastic Dunning prostate tumour subline R3327-AT1. IRT was carried out by the insertion of a single Ir-192 seed into the center of the tumour. For LTH treatments, the tumour-bearing leg was positioned in a circulating constant temperature water bath (43.5 +/- 0.1 degrees C) for 35 min. Neither LTH treatment alone nor the insertion of a dummy seed produced any change in tumour growth compared with sham-treated controls. With regard to the sequence of heating and IRT our results showed that during a 72-h treatment time (30 Gy, 40 cGy/h) a single heat treatment given just before the start of IRT was more efficient (TER = 1.47) in terms of growth delay than LTH given in the middle or the end of radiation treatment (TER approximately 1.0). The growth delay for both the 20 and 40 cGy/h groups appear to be linear with increasing dose for the IRT as well as the IRT + LTH groups. The higher dose-rate was more effective especially with respect to long-term delay in tumour growth in some of the animals. As TER at 40 cGy/h decreased subsequently with increasing treatment time from 1.47 to 1.25 at 60 Gy, we conclude that for treatment times > 72 h, one LTH just before IRT might not be sufficient. If multiple heat treatments are applied during a comparable time course, two LTH treatments one just before the start, the other at the end yielded the greatest local tumour control. In contrast, three LTH given daily were not more effective than the one LTH given just before the start of IRT. These data indicate a clear thermal enhancement of low dose-rate irradiation, with maximal sensitization when hyperthermia was given just before IRT. For multiple heatings a better understanding of the underlying mechanisms of sequencing and timing hopefully provides guidelines how to apply optimally both modalities in the treatment of cancer.
为了确定应用局部肿瘤热疗（LTH）联合组织间低剂量率照射（IRT）的最有效方法，我们研究了诸如辐射剂量率、热疗应用的顺序和频率等因素在间变性邓宁前列腺肿瘤亚系R3327-AT1中的意义。通过将单个铱-192籽源插入肿瘤中心进行IRT。对于LTH治疗，将荷瘤腿置于循环恒温水浴（43.5±0.1℃）中35分钟。与假处理对照组相比，单独的LTH治疗或插入假籽源均未使肿瘤生长产生任何变化。关于加热和IRT的顺序，我们的结果表明，在72小时的治疗时间（30 Gy，40 cGy/h）内，在IRT开始前进行一次热疗在生长延迟方面比在放射治疗中期或末期进行LTH更有效（治疗增益比TER = 1.47）。IRT组以及IRT + LTH组中，20 cGy/h和40 cGy/h组的生长延迟似乎都随IRT剂量增加呈线性变化。较高的剂量率更有效，特别是在一些动物中对肿瘤生长的长期延迟方面。由于40 cGy/h时的TER随后随着治疗时间从60 Gy时的1.47降至1.25，我们得出结论，对于治疗时间>72小时，在IRT前进行一次LTH可能不够。如果在可比的时间过程中进行多次热疗，在开始前进行一次LTH，结束时进行另一次LTH可产生最大的局部肿瘤控制。相比之下，每天进行三次LTH并不比在IRT开始前进行一次LTH更有效。这些数据表明低剂量率照射有明显的热增强作用，在IRT前进行热疗时致敏作用最大。对于多次热疗，更好地理解排序和时间安排的潜在机制有望为如何在癌症治疗中最佳应用这两种方式提供指导。
