Does the combination of hyperthermia with low LET (linear energy transfer) radiation induce anti-tumor effects equivalent to those seen with high LET radiation alone?

Abstract

Introduction: The combination of hyperthermia with low LET (linear energy transfer) radiation may have similar anti-tumor effects as high LET radiation alone. This pre-clinical study determined the optimal heating temperature and time interval between radiation and heat to achieve this equivalent effect. Methods: C3H mammary carcinomas (200 mm3 in size) growing in the right rear foot of CDF1 mice was used in all experiments. Tumors were locally irradiated with graded doses of either 240 kV ortho- or 6 MV mega-voltage X-rays to produce full dose-response curves. Heating (41.0–43.5 °C; 60 min) was achieved by immersing the tumor bearing foot in a water-bath applied at the same time, or up to 4-hours after, irradiating. The endpoint was the percentage of mice showing local tumor control at 90 days, with enhancements calculated from the ratios of the radiation doses causing 50% tumor control (± 95% confidence intervals). Results: Previous published results in this tumor model reported that carbon ions were 1.3–1.7 times more effective than low LET radiation at inducing tumor control. Similar enhancements occurred with a temperature of only 41.0 °C with a simultaneous heat and radiation treatment. However, higher temperatures were needed with the introduction of any interval; at 42.5 °C, the enhancement was 2.5 with a simultaneous treatment, decreasing to a value within the carbon ion range with a 4-hour interval. Conclusions: Combining hyperthermia with low LET radiation can be as effective as high LET at inducing tumor control, but the temperature needed depended on the time interval between the two modalities.