THE OPTIMAL COMBINATION OF HYPERTHERMIA AND CARBOGEN BREATHING TO INCREASE TUMOR OXYGENATION AND RADIATION RESPONSE

Purpose: To determine the most effective combination of carbogen breat hing with mild temperature hyperthermia (MTH) to increase the oxygenat ion and radiation response in murine tumors, Methods and Materials: MT H at 41,5 degrees C for 60 min was applied by immersion of the tumor i n a precisely controlled water bath. The tumor pO(2) was measured with a polarographic microelectrode. The radiation response of the tumor w as determined using the in vivolin vitro assay for surviving tumor cel ls. Results: In the FSaII fibrosarcoma the median pO(2) increased from a control value of 6.5 +/- 0.5 mm Hg to 16.6 +/- 1.1 mm Hg immediatel y after MTH and was 10.9 +/- 1.3 mm Hg 24 h later. Carbogen breathing for 5 min increased the FSaII pO(2) to 19.9 +/- 2.1 mm Hg. Carbogen br eathing for 5 min beginning immediately after MTH increased the median pO(2) more than 5 times to 35.4 +/- 3.8 mm Hg. This combined treatmen t also substantially increased the response of the tumors to a radiati on exposure of 20 Gy, In another tumor model, the SCK mammary carcinom a, MTH treatment increased the median pO(2) from the control level of 4.4 +/- 0.2 mm Hg to 12.6 +/- 1.2 mm Hg, and it returned to 4.3 +/- 0. 3 mm Hg 24 h later, Carbogen breathing for 5 min increased the SCK tum or pO(2) to 17.1 +/- 1.4 mm Hg. The median SCK pO(2) was increased abo ut 7 times to 31.2 +/- 4.2 mm Hg when MTH was followed immediately wit h carbogen breathing for 5 min. The radiation response was also marked ly increased by this combination, When the animals breathed carbogen f or 15 or 30 min, the pO(2) and radiosensitivity in both tumor types ei ther remained the same or was lower than that after 5 min of breathing , In addition, both FSaII and SCK tumors were radiosensitized 24 h aft er MTH treatment alone or with 5 min of carbogen breathing. Conclusion s: A shorter carbogen breathing time immediately after MTH causes the most tumor radiosensitization, The results of this study also demonstr ate that MTH increases radiosensitivity with and without carbogen brea thing up to 24 h after the mild hyperthermia treatment. (C) 1998 Elsev ier Science Inc.