Effects of sequencing of the total course of combined hyperthermia and radiation on the RIF-1 murine tumor.

The optimal sequence for clinical utilization of combined radiotherapy and hyperthermia is not known. The clinical trials have resulted in similar responses whether hyperthermia is given before or after radiation. Moreover, studies addressing the best sequence for an entire course of multifractionated hyperthermia and radiation are lacking. In these experiments, the importance of sequencing of heat and irradiation in a multifractionated treatment regimen in RIF-1 murine tumors was studied. It was observed that a close sequence of heat and irradiation is more beneficial than separate cytotoxic action. When heat and irradiation were given simultaneously, (within 1 hour) 67% to 75% of the tumors were cured. Heat and irradiation given sequentially (the entire course of one following the entire course of the other, each separated by 72 hours) cured 20% of the tumors. No tumors were cured when treated with heat or irradiation alone. The tumor regrowth time (mean tumor doubling time) is much longer in simultaneous treatment than in sequential treatment. It appears that heating first decreases the effectiveness of subsequent irradiation, causing a shorter growth delay than the opposite sequence. Heat alone does not alter the tumor bed permanently, but irradiation seems to do so, resulting in a slower rate of growth upon recurrence.