Development of lymph node and pulmonary metastases after local irradiation and hyperthermia of footpad melanomas

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Abstract
C57BL/6 mice with syngeneic B16-F10 melanomas were treated 7 days after tumor inoculation into the footpad with local hyperthermia (HT) of 43.5°C for 90 min. A combination of local 30 Gy X-irradiation (XRT) given 2, 4 or 12 h after HT cured the primary tumor in 34/35 mice, with irreversible damage to normal foot tissues in most of the animals. When 7.5, 10 or 15 Gy XRT were delivered 4, 18 or 24 h after HT, there were only a small number of cures and also a much smaller incidence of irreversible normal tissue damage. HT alone resulted in a significant (PPdecrease in metastasis to RLN and to the lungs. Conversely, subcurative doses of combined therapy resulted in anincrease in RLN and lung metastasis (PP<0.001). The overall survival of mice treated with HT alone is decreased (P<0.0028). The survival of mice treated with HT followed 4, 18 or 24 h later with 10 Gy XRT is further decreased (P<0.0025). These data show that subcurative HT, or XRT plus HT, increases the incidence of spontaneous metastasis in this syngeneic mouse melanoma model. Curative doses prevent this effect on metastasis, but there is an unacceptable incidence of irreversible damage to the tumor-bearing foot. The cause(s) of this phenomenon are not known.