The therapeutic advantage of combining hyperthermia with x-irradiation to treat tumors depends on whether or not it is possible to achieve greater thermal sensitization of tumors than of normal tissues. To determine such therapeutic gain factors (TGE), we assessed the response of mouse skin and seven transplantable mouse tumors to graded x-ray doses given alone or combined with moderate heat (42.5°C for 60 minutes). We constructed dose response curves for the average early skin reaction and for the induced delay in tumor regrowth to an arbitrarily chosen size. We studied the following areas: 1) the therapeutic gain of combining heat with x-irradiation; 2) irradiation and heat sequencing; 3) vascular occlusion; 4) temperature uniformity; 5) hyperthermia and metastatic spread; 6) fractionated treatment; and 7) thermal tolerance. Our results are not as promising as those of other published studies. We have shown that the time interval between heat and irradiation is important, and we believe that the separate cytotoxic action of heat and x-irradiation is likely to be more beneficial than the synergistic effect of combining the two in close sequence. We have also demonstrated the deficiencies of using hot water to achieve uniform heating, and the possible artefacts of vascular occlusion. We observed no significant effect on the spread of metastases when heat is used adjunctively with x-rays. We also induced thermal tolerance in a mouse tumor, which may account for the loss of therapeutic advantage seen with fractionated treatments
