Session Item

In addition to indirect cell killing through reacting oxygen species (ROS) following stereotactic radiation (SRT)  treatment of tumors, the induction of vascular damage also increases the poor microenvironment conditions within tumors.  Existing evidence suggests that cells under such conditions are more sensitive to treatment with hyperthermia, thus combining heat with SRT should have greater anti-tumor effects.
Objectives: To investigate the potential of combining various hypofractionated schedules with hyperthermia in our C3H mammary carcinoma, which responds to both high radiation doses and heat treatment when injected in the rear leg of our CDF1 mice model.

A C3H mammary carcinoma grown in the right rear foot of CDF1 mice was used when at 200 mm3. SRT (X-rays), involves 1-5 fractions of 5-25 Gy administered in a one-week period. Hyperthermia entails immersing the tumor-bearing leg in a water bath and heating it at 40.5-42.5OC for 60 minutes starting 30-240 minutes after the final irradiation. Endpoints include tumor growth delay (time to 5x treatment volume; TGT5) or local tumor control at 90 days; 3-days after the final radiation a clamped top-up dose was given to produce a dose-response curve from which the TCD50 value (radiation dose controlling 50% of tumors) was determined. Vascular-mediated effects were estimated using dynamic contrast-enhanced magnetic resonance imaging; the endpoint being the initial area under the uptake curve (IAUC). Statistical analysis involved a Student’s T-test or Chi-squared test (p<0.05 for both).

The mean (+ 1 S.E.) TGT5 for control tumors was 5 days (+ 0.2) and this significantly increased to 22 days (+ 0.7) following irradiation with 20 Gy. This radiation dose resulted in a small, yet non-significant, 18% (+ 6) decrease in IAUC, Preliminary studies with an SRT treatment of 3 x 15 Gy resulted in a TCD50 value (+ 95% CI) of 30 Gy (+ 8). Heating tumors at 41.5OC 4-hours after the last irradiation significantly decreased this value to 10 Gy (+ 4).

Conclusions: Our preliminary results with high radiation doses are consistent with some degree of vascular damage and that applying heat after SRT significantly enhanced local tumor control. Additional studies are ongoing to determine the optimal SRT schedule and heat treatment for the greatest anti-tumor response. In addition, the optimal SRT schedules and appropriate temperature would be supplemented with mechanistic studies.