Histopathological changes of human tumors following thermoradiotherapy

Twenty human malignant tumors treated with thermoradiotherapy were examined histopathologically. Hyperthermia was administered regionally with a 13.56-MHz or 8-MHz RF heating device, once or twice a week after irradiation, 2 to 12 sessions in total. Fifteen tumors received a total radiation dose of 26 to 70 Gy in fractions of 1.8 Gy to 2.0 Gy a day, 5 days a week, whereas five tumors received a total dose of 20 to 60 Gy in fractions of 4 Gy each, twice a week. Microscopic examination of 4 of the 20 tumors revealed complete necrosis throughout the cross-section of the entire tumor. All the four tumors had received a total dose of over 60 Gy and a tumor center temperature of over 42 degrees C. In 10 tumors, more than 50% but less than 99% of the cross-section of the entire tumor had massive coagulation necrosis. The remaining six tumors showed relatively little change; the area of intratumor necrosis was less than 50%. The grade of tumor necrosis was dependent on both the temperatures of tumor center and periphery, and a total radiation dose. The small blood vessels and capillaries in the tumor parenchyma were markedly damaged in 16 of the 20 tumors, while the blood vessels in the tumor stroma were damaged in only 2 tumors. Condensation of the destroyed nucleus observed in 15 tumors was considered to be a typical change induced by thermoradiotherapy. Viable tumor cells remained in the tumor central area in only four tumors and around the blood vessels in only three tumors. However, in the tumor peripheral area, viable tumor cells were observed in 16 out of the 20 tumors. These results indicate that histopathological changes induced by thermoradiotherapy are greater in the tumor central area than in the tumor peripheral area, and provide strong rationale for utilizing full dose radiation therapy in combination with hyperthermia as opposed to lower doses for cancer therapy.