THERAPEUTIC RESPONSES OF SPONTANEOUS CANINE MALIGNANCIES TO COMBINATIONS OF RADIOTHERAPY AND HYPERTHERMIA

The goals of this ongoing Phase III study of adjuvant local hyperthermia with radiotherapy were to evaluate how tumor control and normal tissue complications were related to patient and treatment variables. Canine veterinary patients with localized malignancies were stratified by histology and anatomic site and randomized into three groups. All patients received radiotherapy (CO-60) in 3.5 Gy fractions given Mon-Wed-Fri to 14 treatments (49 Gy). One group received radiotherapy alone while the others also received microwave-induced hyperthermia (44-degrees-C) for 30 minutes once each week. Hyperthermia followed radiotherapy and was given to one group immediately and delayed 4-5 hours in the other. Adjuvant hyperthermia resulted in a significant (p < .05) increase in complete response rate, reduction in the frequency of non-responders, and increased persistant local control relative to radiotherapy alone. Hyperthermia increased the complete response rate regardless of histology, site, or volume and with the current sample size control was significantly (p < .05) greater for sarcomas, tumors of the trunk and extremities, and those with volumes < 10 cc. Quantitative clinical assessment of the acute response of skin and oral mucosa indicated that hyperthermia significantly enhanced these acute reactions, which required roughly twice the healing time observed with radiotherapy alone. Quantitative histologic scoring of changes seen between pre-and post-therapy skin biopsies indicated that a treatment induced decline in the frequency of dermal blood vessels, sebaceous glands, and hair follicles was enhanced by adjuvant hyperthermia, particularly in the late response evaluation interval. The probability of tumor control and adverse normal tissue responses correlated with several measures of thermal dose. Thermal doses in excess of 120 equivalent minutes at 43-degrees-C correlated positively with increased skin reactions and negatively with the complete response rate, and these trends were usually evident during the animals' first treatment.