Radiation-induced complications of the rectum are an important dose-limiting factor in radiotherapy of pelvic malignancies. In general, animal studies demonstrated no differences in acute and late normal tissue toxicity with age, but little is known about rectal complications in relation to age. For this purpose, an extensive histological and dose fractionation study was carried out on the rectum of young (12 weeks) and older (77-80 weeks) rats. In this paper, the results of dose fractionation are presented in relation to age at the time of irradiation. Young and older animals were irradiated with single and fractionated doses. After irradiation, rectal complications could lead to occlusion and stenosis, eventually resulting in the clinical symptoms of a megacolon and a possible fistula. For each dose group, cumulative survival rates were obtained with Kaplan-Meier analysis, from which dose-effect curves and the associated LD(50) values for a megacolon/fistula were calculated. The majority of responders died between 8 and 24 weeks after irradiation, irrespective of age. For both age groups, only the fractionation data showed a reduction in the mean latency with increasing dose. In the older age group, 39% of the responders developed a fistula compared to 26% for the younger animals. The LD(50) values increased from around 30 Gy after single doses to nearly 65 Gy after 10 fractions. The increases in LD(50) values with the number of fractions were independent of the age of the rats. For each of the dose fractionation schedules, log-rank testing indicated no significant differences in cumulative survival rates between younger and older animals (P > 0.10). The high alpha/beta ratios obtained for both the young and older animals strongly suggested that the late rectal complications were a consequence of early epithelial injury. Associated histological findings indicated that blood vessel damage, which was already evident at a high incidence at 4 weeks after irradiation, could also play a significant role in the occurrence of consequential late injuries. In conclusion, data obtained for the latent period of rectal occlusion, for the dose-effect curves, for the log-rank testing of cumulative survival rates, and for the alpha/beta ratios strongly support the hypothesis that the incidence of radiation-induced rectal complications is independent of age. Late rectal complications could be a consequence of radiation-induced acute injury.

Temperature distribution is an important factor in thermo-radiotherapy and it is greatly dependent on the applied heating technique. Consistency of the heating method is therefore important in translating in vivo experimental data to the clinical situation. To further evaluate the combination of interstitial hyperthermia and interstitial radiotherapy, an experimental interstitial hyperthermia system has been developed for small (500-2000 mm3) tumours growing in the flank of a rat. The system used reproduces the properties of our clinical current source interstitial hyperthermia system. The heating system consists of four applicators, each with independent tuning and power control. The applicators are situated inside plastic afterloading catheters and are capacitively coupled with the surrounding tissue. The tumour is heated through dissipation of a 27 MHz current flowing to an external ground plane. An effective RF-filter allows reliable thermocouple temperature measurements when the power is switched on. The tumour temperature is easily controlled by means of a continuous temperature read-out and a clear temperature display. A minimum temperature up to 46 degrees C can be reached within 4-10 min and maintained (+/-0.5 degrees C) throughout the treatment period. Modelling calculations performed for this heating system indicate that the applicator temperatures should be kept equal in order to minimize the difference between maximum and minimum temperature. Significantly higher applicator currents are needed at larger distances from the ground plane. In addition, the homogeneity of the temperature distribution is improved when either the tumour is isolated or when the environmental temperature is increased. The calculations also show that temperature distribution is strongly dependent on effective heat conductivity. A description of the system and its performance is presented.

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