Studies were carried out to examine the interactions of local tumor hyperthermia (LTH) with single and multiple doses of fast neutrons as compared to X rays and to gain further information on the possible mechanisms involved in the radiosensitization of tumor tissues. Ridgway osteogenic sarcomas, (1.0 ± 0.1 cm average diameter) grown in both AKR/Jax and <tex-math>${\rm AKD}_{2}{\rm F}_{1}/\text{Jax}$</tex-math> male mice were exposed to single and multiple doses of X irradiation or cyclotron-produced neutrons (Ēn ∼ 3.5 MeV) alone or in combination with LTH (42.5 ± 0.5°C for 15 min). Hyperthermia alone produced a transitory retardation in tumor growth. The RBE of single doses of neutrons alone ranged from 2.6 to 3.0 depending on the endpoint observed. LTH did not appreciably increase the effectiveness of single or multiple doses of neutrons. The effect of a single dose of X rays was enhanced by a value ranging from 1.4 to 1.6 and with multiple doses of X rays the radiation enhancement factor (REF) for LTH ranged from 2.2 to 2.4. The increased killing effect on tumor cells, as a result of X rays combined with heat, probably represents heat-induced inhibition of tumor cell repair and increased radiosensitivity of the hypoxic cell compartment. On this basis hyperthermia when used in combination with fast neutrons and possibly other high-LET radiation thus offers no added advantage to local tumor control.

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