Effects of step-up and step-down heating combined with radiation on murine tumor and normal tissues

Radiosensitizing effects of step-up heating (SUH) and step-down heating (SDH) on the tumor and skin were studied by using mammary adenocarcinoma transplanted to the foot of the C3H/He mouse. The tumor and skin responses were assessed by the tumor growth delay method and the skin reaction scoring method, respectively. Neither SDH (44 degrees, 10 min----42 degrees, 30 min) nor SUH (42 degrees, 30 min----44 degrees, 10 min) alone caused a substantial tumor or skin response. When the heat treatment was given immediately after irradiation, the thermal enhancement ratio (TER) was higher in SDH than in SUH for tumors as well as the skin. A therapeutic gain factor (TGF) of 1.2 was obtained in SUH, while no therapeutic benefit was found in SDH. SDH was applied at various times (0 to 3 hr) before or after irradiation. When SDH was given before irradiation, the TER was consistently high to almost the same degree for tumors and the skin regardless of the time interval, resulting in minimal or no therapeutic gain. With SDH after irradiation, the TER for the skin decreased with increase in the time interval, while the TER for the tumor was moderately enhanced. Therefore, the TGF increased with increase in the time interval and reached 2.2 when SDH was given 3 hr after radiation. SUH is slightly advantageous over SDH in terms of the TGF, and SDH should be given 3 hr after irradiation when selective tumor heating is not possible.