Low dose‐rate irradiation of human glioma cells and thermoradiosensitization by mild hyperthermia

Human brain tumors are clinically very resistant to radiation therapy. Recent clinical trials of combined simultaneous brachytherapy and mild hyperthermia have shown great promise. In this study two relatively radioresistant human glioma cell lines have been irradiated in plateau growth phase under low dose‐rate (LDR) conditions (<1 cGy/min) with and without concurrent mild (39–41°C) hyperthermia. The large degree of LDR sparing observed at 0.88 cGy/min (LDR1) was almost completely inhibited by concurrent heating at 41°C, resulting in a thermal enhancement ratio (TER) of 1.6 and 1.8 at the 1% survival level for U‐87MG and U‐373MG, respectively. At 0.41 cGy/min (LDR2) concurrent heating at 41°C resulted in greater thermoradiosensitization for U‐87MG (TER 2.1) and less thermoradiosensitization for U‐373MG (TER 1.5). For U‐87MG, thermoradiosensitization with LDR2 at 39 and 40°C was similar and suboptimal compared with concurrent 41°C hyperthermia. For U‐373MG, thermoradiosensitization was nearly absent at both 39 and 40°C. The direct cytotoxicity of 39, 40, and 41°C heating was similar in both cell lines. Survival after 48 hr of heating at 41°C was not less than 30% for either cell line. Hyperthermia delivered prior to LDR irradiation has shown varying degrees of sensitization both in vitro and in vivo. In this study, preheating with 8 hr at 41°C did not sensitize 9 Gy LDR2 at 37°C; however, 1 hr at 43°C did result in some thermoradiosensitization with a survival reduction factor (SRF) of 1.4. With 9 Gy LDR2 delivered at 41°C, preheating did result in additional thermoradiosensitization (SRF of 1.6, 3.5, respectively). The significant degree of thermoradiosensitization seen with concurrent LDR irradiation and 41°C hyperthermia with or without preheating supports the promising results seen in recent clinical trials.