Forty-three dogs with primary malignant melanoma were randomized to receive radiotherapy alone (XRT) or hyperthermia plus radiotherapy (delta + XRT). Tumour responses were analysed in terms of complete response rates, rate of one year disease free survival and the incidence and time to develop distant metastasis. The frequency of complete responses (CR) was greater with adjuvant heat (76 per cent vs 21 per cent for XRT; P = 0.001). A trend towards an improvement in one year disease free survival was observed with delta + XRT (23.8 per cent) as compared with XRT (7.7 per cent), but the difference was not statistically significant. The frequency of distant metastases was not different between the two treatments. Descriptors of intratumoural temperatures achieved during therapy indicated that higher CR rates could be achieved with higher minima. When minima were less than and greater than 20 Equivalent minutes at 43 degrees C (Eq43) the CR rates were 64 and 90 per cent, respectively. One year disease free survival rates and frequencies of distant metastases seemed to be correlated with the intratumoural temperatures as well. This was reflected in analyses examining temperature minima and maxima. Examination of patterns of failure suggested that the most plausible explanation for the correlation between intratumoural temperature and metastases was the high local failure rate (70 per in the heated group). The results of this study emphasize the need for further investigation of the influence of local hyperthermia as a part of curative therapy on the frequency of distant metastases.

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Experiments were performed to determine the dose-related effects of the intravenous administration of a vasodilator (hydralazine) on normal muscle blood perfusion during localized hyperthermia. Fourteen anaesthetized outbred canines were investigated, seven receiving the recommended dose level of 0.5 mg/kg and seven receiving one-quarter of that level. The changes in blood perfusion were estimated using two methods: calculation of an effective blood perfusion magnitude and the use of state and parameter estimation techniques. Both methods showed that the changes in blood perfusion induced by the hydralazine were significant, and that the differences between the results for the two drug doses were not significantly different. This suggests that low doses may be useful in humans, giving the same resultant blood perfusion increase but with a decreased patient risk relative to standard therapeutic doses of hydralazine. While the trends in the blood perfusion changes were the same for both calculation methods the effective perfusion method frequently yielded blood perfusion magnitudes significantly different from those obtained using the state and parameter estimation technique. The differences are postulated to be due to the fact that the effective perfusion values include conduction effects, thus overpredicting the amount of perfusion present. Thus, while the effective blood perfusion can be used as a qualitative indication of blood perfusion changes under certain conditions, we do not recommend its use as a quantitative measure of perfusion.

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