Inr J Radr olw n O,,c,,lo~ ~ Bloi Phrr Vol. 20. pp. 1281-1286 0360-3016/ 91 $3.00 + .Ml Pnnted !n the U.S.A. All rights reserved. Copyright (c. I99 I Pergamon Press plc ?? Original Contribution COMBINED TREATMENT WITH INTERSTITIAL HYPERTHERMIA AND INTERSTITIAL RADIOTHERAPY IN AN ANIMAL TUMOR MODEL ARNOUT C. C. RUIFROK, PH.D., PETER C. LEVENDAG, M.D., PH.D., ROBERT F. LAKEMAN, B.Sc., INGERXARINE K. DEURLOO, M.Sc. AND ANDRIES G. VISSER, PH.D. Dr.Daniel den Hoed Cancer Center, Departments of Radiation Oncology and Radiation Physics, Groene Hilledijk 30 1, 3075 EA Rotterdam, The Netherlands 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 RI 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°C for 30 minutes was delivered by controlling the temperature at the periphery of the tumor to 44°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 Ir19*wires with an average activity of 4.5 - 10’ 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 (GDl) of 6 + 2 days without significant reduction of tumor volume. The 50% tumor cure dose after interstitial radiotherapy alone was 95 f 9 Gy. Combination of interstitial hyperthermia and interstitial ra- diotherapy resulted in reduction of the 50% tumor cure dose to 48 rt 13 Gy. The dose-effect data for cure for these modalities are compared to existing data for external irradiation andexternal 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 tem- peratures; in the combined modality experiments a thermal enhancement factor of 2.0 f 0.3 (mean f standard deviation) was observed. Interstitial hyperthermia, Interstitial radiation, Rhabdomyosarcoma, Animal tumor model. INTRODUCTION Treatment with heat, especially in combination with ra- diation, has a significant effect on the growth of tumors (8, 15). Heat delivery to deep seated tumors by external applicators remains technically difficult; to solve this problem, heating by interstitial techniques has been pro- posed. At the Dr. Daniel den Hoed Cancer Center, an interstitial hyperthermia (IHT) system with thin, flexible heating applicators of variable length, operating at 27 MHz, has been developed, that is fully compatible with interstitial radiotherapy (IRT) afterloading systems (19). Some in vitro experiments suggest that the potentiating effect of heat is dose-rate dependent, with the greatest effect when the IHT is combined with low-dose-rate irradiation (5,7,9, 12). Moreover, as most IRT treatments make use of low-dose-rate irradiation, the combination of IHT with IRT seems logical from a radiobiological as well as from a logistic/technical point of view. We studied the feasibility of this newly designed 27 MHz heating system in an in vivo animal tumor model; also, experiments were per- formed in order to obtain information on the effectiveness of combining IHT and IRT using the same animal tumor model. METHODS AND MATERIALS Experimental tumor system The experimental tumor system used is a transplantable rhabdomyosarcoma (R- 1 ), originally derived from an isologous undifferentiated rhabdomyosarcoma (2,3). De- tails about origin, growth characteristics, and radiosen- sitivity have been published elsewhere (2-4, 17, 18). Small pieces of tumor of about 2 mm3 were implanted subcu- taneously in the left flank of 14-week-old female rats of an inbred Wag/Rij strain. Tumor treatments were started Reprint requests to: Dr. P. C. Levendag. Accepted for publication 14 December 1990. 1281