Biological Cell Survival Mapping for Radiofrequency Intracavitary Hyperthermia Combined with Simultaneous High Dose‐rate Intracavitary Irradiation

Abstract

We examined the best way to combine recently developed radiofrequency intracavitary hyperthermia with simultaneous high dose-rate intracavitary brachytherapy in an original experimental model. Temperature distribution was measured with an experimental phantom which was immersed in a water bath with the temperature controlled at 37°C. Radiation dose distribution was calculated with a treatment-planning computer. Cell survival was measured by colony assay with HeLa-TG cells in vitro. Radiation dose response at 1-7 Gy and time response with hyperthermia in the range of 40-46°C were estimated. Radiation dose-response curves in simultaneous treatment with hyperthermia for 30 min at 37 to 46°C were estimated and the surviving fractions in combined treatment were plotted against temperature. For intracavitary radiation alone, cell survival rates increased with increasing distance from the source. For intracavitary hyperthermia alone, the maximum temperature was observed at a depth of 13 mm from the surface of the applicator under suitable treatment conditions. Homogeneous cell killing from the surface of the applicator to a tumor depth of 13 mm was observed under a specific treatment condition. Our experimental model is useful for evaluating the best simultaneous combined treatment. Key words: Intracavitary hyperthermia -Intracavitary brachytherapy -High dose-rate irradiationRadiofrequency hyperthermia -Experimental studyThe most effective combination of radiation and hyperthermia is considered to be simultaneous exposure, rather than sequential treatment.1, 2) However, external hyperthermia combined with simultaneous external irradiation for deep-seated tumors is difficult in clinical practice because it requires special devices.3-5) When simultaneous treatment can be applied to deep-seated tumors, an intracavitary or interstitial approach is probably necessary. A combination of recent developed radiofrequency (RF) intracavitary hyperthermia and intracavitary high dose-rate irradiation with iridium-192 sources seems to be a good method for simultaneous exposure to treat deep-seated advanced tumors.Although simultaneous treatment is theoretically attractive, quantitative data on temperature distribution under various heating conditions and on cytotoxicity, including hyperthermic radiosensitization, are not available. The aims of this study were therefore to collect temperature data on radiofrequency intracavitary hyperthermia with an original phantom under various heating conditions and to obtain cell survival maps in the case of simultaneous treatment with an in vitro experimental system. Finally, we investigated the conditions giving the most uniform cytotoxic effect, which should be the best for combined intracavitary hyperthermia and intracavitary radiation treatment. MATERIALS AND METHODSTemperature measurement in RF intracavitary hyperthermia A phantom was used for measuring temperature distribution (Fig. 1). An Endoradiotherm 100A (Olympus, Tokyo) operating at 13.56 MHz was selected as a device for intracavitary...