Studies of murine tumor control using x-ray fractionation schedules alone or in combination with hyperthermia

The effectiveness of an experimental radiation fractionation schedule of decreasing-sized dose fractions administered at optimal time intervals was compared with a conventional fractionation schedule of constant-sized dose fractions administered five times per week. Also, the effect of the addition of hyperthermia (42.50C) to radiation therapy was investigated. For some experiments, Ehrlich mammary tumors were growth in the right thighs of Swiss mice. The tumor response was determined by measuring the tumor-bearing leg diameter and converting this value to volume. The time for the treated tumor to regrow to its pre-tratment volume was used as an endpoint in Swiss mice. The maximum total treatment dose is limited by the amount of normal tissue damage. A total treatment dose of six thousand rads was most suitable for the further investigations. Definitive investigations were performed using the RIF-1 tumor grown in the right thigh of C3H mice. The length of mitotic delay of RIF-1 cells, in vivo, was determined after various single doses of x radiation. A direct (exponential) relationship betwen x-ray dose and mitotic delay time was observed. Times of release of the RIF-1 cells from radiation-induced mitotic delay were used to determine the optimum time intervals to deliver the decreasing-sized dose fractions. Six thousand rads administered as decreasing-sized dose fractions resulted in significantly greater RIF-1 tumor control, as compared to conventional radiation therapy. The best treatment schedule, overall, was decreasing-sized dose fractions plus hyperthermia