Total-body hyperthermia versus primary tumor hyperthermia in the treatment of the rabbit VX-2 carcinoma.

Abstract

The respiration of rabbit VX-2 carcinoma cells heated in vitro increased at temperatures between 37.5° and 40.0° and was inhibited after 2 hr at 42.0°. Anaerobic glycolysis of the cells, in the presence and in the absence of added glucose, was unaffected by elevated temperature. The O2 uptake of metastatic VX-2 cells isolated from involved lymph nodes was significantly depressed but not completely inhibited by 42.0° in vitro . Established VX-2 tumors were treated by local hyperthermia (water bath immersion of the tumor-bearing hind limb) or by total-body hyperthermia (radiant heating of the rabbit). In each case, the intratumor temperature was maintained above 42.0° for 1 hr on Days 35, 36, and 37 following tumor inoculation, the fractionated therapy being completed within the mean generation time of the tumor cells. There was a significant difference in the regression rates of tumors treated by the two methods. In the case of local heating, tumor volume was halved every 0.97 week from the 2nd week following treatment while, after total-body heating, tumor volume was halved every 2.9 weeks over the same period. Four of 8 rabbits treated by primary tumor hyperthermia are alive 2 years after heating, whereas only 1 of 14 animals treated by total-body hyperthermia is alive 1 year after therapy; all control rabbits died with lung and lymph node metastases at 70 ± 6 days after tumor-cell inoculation into the limb. Intrathoracic and intraabdominal thermocouple sensors indicated that central body (core) temperature of the rabbits fluctuated considerably over the period of total-body heating, with an average temperature in the region of 40°. It is suggested that the inability to maintain a central body temperature of 42° may have contributed to the failure of total-body hyperthermia to increase animal survival. Stimulation of metastatic cells by the 40° central body temperature is a possibility, but a different response of the immune system of the tumor-bearing host to the two types of heating also requires consideration.