Antitumour effect of irradiation followed by hyperglycemia and hyperthermia: the dependence on tumour size and blood flow.

Abstract

The interrelationship of three tumour parameters-volume, blood flow and growth delay-was evaluated after irradiation alone or combined with hyperglycemia (HG) and hyperthermia (HT). The experiments were performed on Ehrlich carcinoma tumours 5, 7 or 9 days after intramuscular implantation when they reached a mean volume of approximately 0.17, 0.46 or 0.90 cm3, respectively. Tumours were irradiated at a dose of 12.5 Gy. In groups of trimodality therapy, induction of HG (5i.p. injections of glucose during a 2-h period, total dose of glucose 10.4 g/kg) was started immediately after irradiation, and HT (water bath, 43 degrees C, 30 min) was given 3 h later. Regardless of the method of therapy, blood flow in the central part of each tumour was measured 4 and 7 h after irradiation by 133Xe clearance technique. It was shown that if tumours were treated by irradiation alone, both tumour blood flow and growth delay declined with increasing tumour volume. There was no correlation between individual values of tumour blood flow intensity and growth delay within each size group, and only all the data pooled together showed a significant direct relationship between these two parameters. In contrast, for radiotherapy with HG and HT, the antitumour effect increased with tumour volume. Blood flow was strongly inhibited by radio-modifiers; the larger tumours, the lower levels of perfusion were observed. There was a pronounced trend of increased tumour growth delay with decreased blood flow for tumours of the same volume, and these parameters were highly correlated if all individual data were analysed together regardless of tumour size. It was concluded that postirradiation blood flow inhibition plays a significant role in the tumouricidal effect of irradiation with HG and HT. The monitoring of tumour perfusion may be useful for the prediction of the effectiveness of such postirradiation modification, which is especially attractive in radiotherapy of large advanced tumours.