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Abstract
The effects of localized hyperthermia (HT) in combination with low dose rate irradiation (brachytherapy) have been investigated in vivo using a murine mammary adenocarcinoma. Flank tumours were grown to 0.45–0.70 cm3 in volume, at which time their treatment course was initiated. Tumours were locally heated in a water bath for 15 min at either 44 or 45°C. For tumour irradiations a non-invasive cap was devised to permanently house three iodine-125 sealed sources located at 120° intervals around the circumference of the hemispherical cap. During treatment, mice were secured in a modified syringe tube allowing mobility while restricting access to the cap which was placed over the tumour. Calculated dose rates ranged from 15 to 40 cGy/h. Brachytherapy (BT) was delivered for 48 or 72 h to obtain a dose range of 830–2378 cGy. Mice were randomized into one of 10 treatment protocols: BT alone, HT-BT, BT-HT, HT-BT-HT, 1/2BT-HT-1/2BT, four control groups of HT alone and a sham treatment group. Normalized tumour doubling volume growth delays (GDDv) were used to calculate the thermal enhancement ratios (TER). In the 44°C experiments, HT before BT (TER= 1.33 ±0.071) was more efficacious than HT after BT (TER=1.07 ±0.042). Two HT treatments, one given before and one after BT (TER = 1.38 ± 0.152), were not different from a single HT treatment given before BT. However, a single HT treatment given in the middle of an interrupted course of BT resulted in the greatest thermal enhancement (TER=1.64±0.072) compared to any other treatment sequence. These data suggest that potentiation of low dose rate irradiation by a single heat treatment may be maximized if the HT is given either in the middle of, or simultaneously with, the BT.
