WE-FG-BRA-03: Oxygen Interplay in Hypofractionated Radiotherapy: A Hidden Opportunity




Local oxygen during a radiotherapy fraction has been shown to change over a full range of the oxygen enhancement ratio (OER) during the same time scale as the treatment fraction. Interplay with local oxygen is then likely a concern, especially for hypofractionation. Our experiments that show a strong role for metabolic dynamics suggesting one could manipulate this interplay for more efficacious treatments.


Two published experiments are presented with the same human head and neck cancer cell line (UM-SCC-22B). One is a cell-specific in vitro prompt response to a 10 Gy dose of orthovotage radiation using fluorescence lifetime imaging (FLIM), benchmarked with a Seahorse assay. The other in vivo study uses autocorrelation analysis with blood oxygen level dependent magnetic resonance imaging (MRI-BOLD) on xenografts. In vivo results are verified with diffuse optics using spectra fitting and photoacoustic measurements. All these measurements are at high time resolution: sampling is one per minute.


Interplay happens when the radiosensitivity modulates at the same time scale as the radiation. These results show dynamics at these time scales. 1. The dominant time scale of the acute hypoxia in cell line xenografts is shown to be on the order of minutes to tens of minutes: similar to a metabolic oscillation known as the ‘glycolytic oscillator.’ 2. The radiation dose itself alters metabolism within minutes to tens of minutes also.


These results vary with cell type. There is a possibility that special timing and dose levels could be used for radiation. Gating could be used for maximal oxygen during treatment. There is an analogy to the interplay discussions with tumor motion, except that an oxygen interplay could more likely be patient-specific at a more fundamental level.