Response of canine soft tissue sarcomas to radiation or radiation plus hyperthermia: a randomized phase II study

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Abstract
Sixty-four dogs with spontaneous soft tissue sarcomas without evidence of metastases were stratified by tumour volume and randomized to receive graded doses of radiotherapy (XRT) alone or radiotherapy plus hyperthermia (HT). An improvement in duration of local control was achieved with the addition of hyperthermia as compared with XRT alone (Wilcoxon, p = 0.040; log rank, p = 0.064). Overall frequency of late complications was not different for the two treatment arms when comparing across equivalent XRT dose groups. Frequency of distant metastases after therapy completion was not significantly different for the two treatment arms at 1 year (7.4% for XRT versus 20% for HT plus XRT) or 2 years (11.5% for XRT versus 25% for HT plus XRT) post therapy. These results suggest that a therapeutic gain was achieved for this group of tumour-bearing animals. Uni- and multivariate analyses were performed to examine the potential for various factors to influence treatment outcome. Patient related variables included tumour stage, histologic subtype and grade and tumour site. Treatment related variables included total radiation dose and 15 descriptors of temperature distributions achieved during hyperthermia. When considering patient related factors, tumour histology, grade and location were important predictors of time to minimum volume, but only tumour location influenced time to tumour regrowth. When considering treatment related factors, radiation dose was not significantly correlated with time to minimum volume or time to local regrowth, but it was correlated with probability for late normal tissue damage in the XRT alone group (p = 0.005). For the hyperthermia treatments, 13 of 15 tumour temperature distribution descriptors were correlated with time to minimum volume, but none were correlated with time to local regrowth. These results suggest that caution should be used in interpreting the value of temperature distribution descriptors in predicting for long-term local control after hyperthermia and radiotherapy, based on analysis of short-term responses.