Combined treatment with interstitial hyperthermia and interstitial radiotherapy in an animal tumor model

An interstitial hyperthermia system operating at 27 MHz has been developed at the Dr. Daniel den Hoed Cancer Center. To test this system in combination with interstitial radiotherapy and to study the interactions of interstitial radiotherapy and interstitial hyperthermia, animal experiments were performed using rhabdomyosarcoma type R1 transplanted in the flanks of female Wag/Rij rats. Using the 27 MHz system, it appeared feasible to obtain hyperthermic temperatures. In this experiment a thermal dose of 44 degrees C for 30 minutes was delivered by controlling the temperature at the periphery of the tumor to 44 degrees C. The interstitial heating applicators were inserted in four standard afterloading catheters implanted with a fixed spacing of 7 mm; the same catheters were used for the radioactive sources for interstitial radiotherapy treatment following the interstitial hyperthermia sessions. Interstitial radiotherapy was given by means of four Ir192 wires with an average activity of 4.5.10(7) Bq/cm. Minimum tumor doses of 20 to 115 Gy with a mean dose rate of 47 cGy/hour were applied. Interstitial hyperthermia alone resulted in a growth delay (GD1) of 6 +/- 2 days without significant reduction of tumor volume. The 50% tumor cure dose after interstitial radiotherapy alone was 95 +/- 9 Gy. Combination of interstitial hyperthermia and interstitial radiotherapy resulted in reduction of the 50% tumor cure dose to 48 +/- 13 Gy. The dose-effect data for cure for these modalities are compared to existing data for external irradiation and external hyperthermia in the same tumor model. It was found that the addition of hyperthermia to different modes of irradiation, that is, either to single dose or protracted radiotherapy, results in a common level of radiosensitivity through impaired repair of sublethal damage. This study demonstrates the feasibility of the 27 MHz heating system in achieving hyperthermic temperatures; in the combined modality experiments a thermal enhancement factor of 2.0 +/- 0.3 (mean +/- standard deviation) was observed.