The effect of hyperthermia on radiation carcinogenesis was investigated in the C3Hf/Sed mouse foot. The foot was irradiated under hypoxic conditions, in air, or under hyperbaric oxygen conditions to evaluate the oxygen effect. Hyperthermia at 43.5 degrees C for 45 min was given by immersing the animal foot into a constant temperature water bath. A malignant tumor in the irradiated foot was first observed congruent to 250 days after irradiation. Tumors developed in the irradiated area until day 850. RCD50, or 50% radiation carcinogenesis dose was the endpoint and was calculated based on the tumor incidence 650 days after irradiation. RCD50 following radiation given alone under hypoxic conditions was 66.3 (60.0-73.2) Gy, and the oxygen enhancement ratio (hypoxic/hyperbaric oxygen) was 3.0 (2.5-3.5). Radiation carcinogenesis was enhanced by hyperthermia given with a 20 min treatment interval with no significant alteration in the oxygen effect. Thermal enhancement was greatest when hyperthermia was given 20 min prior to irradiation (2.5 [2.2-2.9] under hypoxia). No thermal enhancement was observed when two treatments were given with a treatment interval of 2 days. The median time to develop a malignant tumor decreased with increasing radiation dose. This median time was shorter following combined hyperthermia and irradiation (423 days) than following radiation alone (504 days). Histological studies revealed that more than 80% of tumors were soft tissue sarcomas, and the most common tumor was fibrosarcoma. Squamous cell carcinoma was found in 7% of all tumors.

Urano, Kenton, Kahn, , , , , , (1989). The effect of hyperthermia on the early- and late-appearing mouse foot reactions and on radiation carcinogenesis: Part II. Effect on radiation carcinogenesis (thermal enhancement and oxygen enhancement). International journal of radiation oncology, biology, physics, 1989 Feb;16(2):437-42. https://www.ncbi.nlm.nih.gov/pubmed/2921146