Influence of thermotolerance on the interaction between hyperthermia and radiation in a solid tumour in vivo.

The influence of thermotolerance (i.e. a temporary resistance to a subsequent heat treatment induced by prior heating) on the response of a C3H mouse mammary carcinoma to combined water-bath hyperthermia and radiation was investigated. Prior heating at 43.5 C for 30 min induced thermotolerance which was at a maximum 16 h later and had completely disappeared after 120 h. Prior heating reduced tumour response to simultaneous heat and radiation given 16 h later, as evidenced by a reduction from 5.1 to 3.3 in the thermal enhancement ratio (TER). The effect was lost by 120 h. This indicates that development of thermotolerance reduces the degree of thermal radiosensitisation. However, although the time course was the same, the prior heating effect on the combined treatment was smaller than on the resistance to heat alone. With sequential treatment, the tumours were treated with X rays (28 Gy) followed four hours later by a two-dose heat treatment at 43.5 degrees C, the first for 30 min and the second after an interval of 0, 16 or 120 h. With this treatment thermotolerance fully manifested itself. It was necessary to increase the duration of heating when applied 16 h after prior heating by a factor of 5.4 to cause a TER of 2.0, a value not significantly different from the expected value of 5.2, i.e., the thermotolerance ratio for heat alone.