Timing and sequence of hyperthermia in fractionated radiotherapy of a murine fibrosarcoma.

OBJECTIVE

This study investigated the effect of timing and sequence of hyperthermia on fractionated radiotherapy, since it has been shown that the heat increases the size of hypoxic cell fraction which could affect the effect of subsequent radiation doses.

METHODS

Animal-tumors were early generation isotransplants of a spontaneous fibrosarcoma, FSa-II, in C3Hf/Sed mice. Tumor response was studied by tumor growth time and TCD50 (50% tumor control dose) assays. The tumor growth time is the time required for one-half of the treated tumors to reach 500 mm3 from the first treatment day. The TCD50 is a radiation dose to control one-half of the treated tumors for 120 days following treatments. One heat treatment at 43.5 degrees C for 45 min was given in a water bath in combination with fractionated doses independently (24 hr interval) or simultaneously (2 min interval). For the normal tissue study, the mouse foot was treated, and the acute foot reaction was scored daily and averaged. The late foot reaction was scored in animals used in the TCD50 assay that developed no recurrence for 120 days. The RD50(2.0) and RD50(5.0), or total radiation doses to induce an average score of 2.0 (complete epilation) and 5.0 (partial foot atrophy) in 50% of treated animals, were calculated.

RESULTS

Thermal radiosensitization was most prominent when heat was combined simultaneously with the first or last radiation dose in both the tumor growth time and TCD50 assays. However, the thermal enhancement was greatest when heat was given either with the first or last radiation dose in the TCD50 assay; whereas it was greatest when heat was administered with the last radiation dose in the tumor growth time assay. Both acute and late skin reactions were significantly potentiated by heat administered 24 hr before the first radiation dose.

CONCLUSIONS

A significant observation in this study was that, in both the tumor growth time and TCD50 assays, heat given independently or simultaneously did not result in any therapeutic gain compared to the radiation alone treatment.