Variations in$p{\rm O}_{2}$ and pH Response to Hyperthermia: Dependence on Transplant Site and Duration of Treatment

It has been clearly established that changes in intratumor$p{\rm O}_{2}$ and pH occur following hyperthermia, and it has been hypothesized that these changes may, in some way, be related to the ultimate response (i.e., cure) of the lesion. The purpose of this study was twofold: first, to examine the changes in intratumor pH during the course of a hyperthermia treatment at biologically related end point "does"; second, to examine the response of$p{\rm O}_{2}$ after treatment in a different lesion transplant site. During hyperthermia treatment of the tumor transplanted in the leg, intratumor pH was found to drop from a control value of 6.74 ± 0.17 to 6.47 ± 0.13 within 15 min following the start of treatment. The values then remained relatively constant throughout the remainder of the treatment (either 1 or 2 h at 43.5°C). Following the subcurative (10% tumor cures at 30 days; 60 min at 43.5°C) treatment the pH began to rise immediately, while after the higher dose (60% tumor cures at 30 days; 120 min at 43.5°C) a slight rise in pH was followed by a continuous drop in pH for up to 4 h, as we have reported previously. Oxygen response in the two transplant sites (leg and flank) was found to be remarkably different even though the tumor cure rate was identical for a given hyperthermia "dose" in terms of time and temperature. In the leg, only very low levels of oxygen can be measured in the tumor 24 h after treatment with either "dose" studied (all measured$p{\rm O}_{2}$ values ≤5 mm Hg). In the flank, the tumor response is dependent on hyperthermia "dose." Only 28% of measured oxygen values are ≤5 mm Hg 24 h following a subcurative "dose," while 4 h following the higher "dose" there is a nonsignificant trend toward hypoxia (∼65% of values ≤5 mm Hg) with a subsequent shift toward reoxygenation. These latter observations are contrary to results reported previously and tend to contradict some current theories regarding the physiological mechanisms associated with hyperthermia treatment.