Author: Beverly Allen, Jay C. Buckey, David J. Gladstone, P. Jack Hoopes, David I Hunter, Armin Tavakkoli 👨🔬
Affiliation: Thayer School of Engineering, Dartmouth College, Geisel School of Medicine, Dartmouth College, Geisel School of Medicine, Thayer School of Engineering 🌍
Purpose: Hyperbaric oxygen (HBO) therapy immediately prior to radiation therapy has been proposed as treatment to enhance radiosensitivity of hypoxic tumors. A murine glioblastoma model was utilized to evaluate the efficacy of pre-irradiation HBO therapy in improving tumor control. Local oxygen dynamics within tumor tissue were also characterized during and after HBO treatment.
Methods: Mice (N=40) were injected with SB28 glioblastoma cells in their left flank to induce tumor growth. Mice were randomized into four groups of equal mean tumor size (n=5): (1) radiation plus HBO therapy, (2) radiation only, (3) HBO only, and (4) no HBO. HBO therapy was administered at 19.1 psi for 90 minutes. A Varian Trilogy linear accelerator simultaneously irradiated mice with 25 Gy of 6 MV photons at 10 Gy/min using 5, 1x1cm fields. Time between concluding HBO therapy and irradiation was 7 minutes. Tumor growth was monitored 3x/week for 4 weeks and mice were removed from study when tumor volume exceeded 500mm3. In a separate cohort (n=3), oxygen measurements were obtained from the tumor during and after HBO therapy using tumor injected PdG4.
Results: No significant difference was observed in tumor control between the HBO therapy plus irradiation and irradiation only groups. Irradiation significantly slowed tumor growth compared to HBO only and no HBO. Oxygen measurements demonstrated the tumors to be hypoxic and that oxygen levels returned to the hypoxic baseline rapidly during chamber depressurization.
Conclusion: HBO therapy immediately prior to irradiation did not improve the radiosensitivity of the murine glioblastoma model. We show that the poorly vascularized tumors returned to hypoxic conditions rapidly upon HBO chamber depressurization, diminishing a pO2 linked radio-sensitization effect between HBO and non-HBO mice. Future work should evaluate tumor oxygenation dynamics during HBO in large animal models to determine if appreciable sustained increases in oxygenation offer enhanced radiosensitization.