To best use hyperthermia with radiotherapy in the treatment of cancer it is essential to determine optimal methods for combining these treatments and to identify which patients will derive the greatest therapeutic benefit. The purpose of this study is to evaluate the efficacy of local tumor control and quantitate the magnitude and characteristics of acute and late normal tissue changes when curative intent radiotherapy is combined with therapeutic hyperthermia in a prospective randomized trial using spontaneous tumors in companion animals (canine and feline) as a model system for human cancer therapy. Dogs and cats with spontaneous tumors referred to us by local veterinarians will be stratified by histology and randomly assigned to one of three protocol groups. Each group will receive thrice weekly tumor radiation doses of 3.5 Gy to a total of 14 treatments. Two of the groups will, in addition, receive 5 weekly hyperthermia treatments targeted to 44 degrees C for 30 minutes where radiation will precede hyperthermia either immediately or 4-5 hours post-irradiation. All treatments will be administered under general anesthesia. Radiotherapy treatments of standardized anatomic zones containing the tumor will be administered using the radiotherapy modality (60 Co or linac photons) giving the most uniform dose distribution. Hyperthermia treatments will be administered with a Clinitherm Mark VI clinical microwave hyperthermia unit using either external or interstitial antennas. Treatment temperatures will be monitored within the tumor and surrounding normal tissue by up to 12 interstitial fiberoptic sensors. Each treated animal will be followed for 2 years to quantitate: the degree of tumor response, the frequency of tumor recurrence, the characteristics, frequencies, and magnitudes of acute and late changes within treated normal tissues and within the tumor bed, and the time following treatment commencement when these effects are observed. These results will be analyzed by appropriate statistical methods in a manner designed to demonstrate how the relationships between the treatment administered, and the acute and late normal tissue changes and the tumor response and recurrence rates are affected by the major identifiable variables including tumor histology, volume, anatomic site and thermal dose. This analysis will demonstrate those changes in acute and late normal tissue complications that occur when heat is combined with radiation, as well as to help establish prognostic factors which can be used to plan appropriate combined treatments for a variety of clinical cancer management situations.
