Glucocorticoids modulate tumor radiation response through a decrease in tumor oxygen consumption. Commentary

Purpose: We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO 2 ) through inhibition of mitochondrial respiration. Experimental Design: The effect of three glucocorticoids (hydrocortisone, dexamethasone, and prednisolone) on pO 2 was studied in murineTLT liver tumors and FSall fibrosarcomas. At the time of maximum pO 2 (t max , 30 min after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO 2 measurements were done using electron paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo glucocorticoid administration was measured using high-frequency electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging. Results: All glucocorticoids tested caused a rapid increase in pO 2 . At t max , tumor perfusion decreased, indicating that the increase in pO 2 was not caused by an increase in oxygen supply. Also at t max , global oxygen consumption decreased. When irradiation (25 Gy) was applied at t max , the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7). Conclusion: These results show the potential usefulness of the administration of glucocorticoids before irradiation.