An investigation of oxygen enhancement ratio modeling for proton dose calculation

Range uncertainty due to variations in the relative biological effectiveness is considered a significant issue in proton therapy. This study aims to investigate the effects of the hypoxic fraction of a tumor volume and its fractionation effects on the oxygen enhancement ratio (OER) in the OER modeling of proton beams. We calculated OERs for proton beams in relation to increases in the hypoxic tumor volume. A voxelized three-dimensional cell modeling was used to calculate the oxygen tension for each voxel. The linear energy transfer (LET) and dose distributions were fixed for each round of calculation. Linear-quadratic (LQ) and universal-survival curve (USC) models were used to compare the effects of the hypoxic fraction of a tumor volume in four clinical cases: chordoma, prostate, lung, and head and neck. In addition, the fractionation effect on the OER was investigated for static and local oxygenation change (LOC) scenarios. The OERs obtained using the LQ model for fractions between 3 and 9 were in the range of 2.12-2.44 with an LET of 3 keV/mu m. The OERs obtained using the USC model showed no significant difference from those obtained using the LQ model. The increasing values of OER obtained with increasing hypoxic tumor volume did not appear to depend on the tumor type. The OER increased with a decrease in the number of fractions (increase in fraction dose) in our model. The LOC was also found to reduce the OER values as opposed to static cases. The OER for proton beams may be increased in hypo-fractionation in case of a large hypoxic tumor volume. The OER should be considered to optimize treatment dose calculation, especially for hypo-fractionated regime in proton beam therapy.