Effects of intra-tumoral cellular heterogeneity of oxygen partial pressure on biological effectiveness of hydrogen-, helium-, carbon-, oxygen-, and neon-ion beams.

The tumor microenvironment characterized by heterogeneously organized vasculatures causes intra-tumoral heterogeneity of oxygen partial pressure at the cellular level, which cannot be measured by current imaging techniques. The intra-tumoral cellular heterogeneity may lead to a reduction of therapeutic effects of radiation. The purpose of this study was to investigate the effects of the heterogeneity on biological effectiveness of H-, He-, C-, O-, and Ne-ion beams for different oxygenation levels, prescribed dose levels, and cell types. Approach. The intra-tumoral cellular distributions were simulated with a numerical tumor model for average oxygen pressures ranging from 2.5 to 15 mmHg. The relative biological effectiveness (RBE)-weighted dose distributions of 3-15 Gy prescribed doses were planned for a cuboid target with the five ion species for constant values. Radiosensitivities of human salivary gland tumor (HSG) and Chinese hamster ovary (CHO) cells were investigated. The planned dose distributions were then recalculated by taking the heterogeneity into account. Main results. As decreased and prescribed dose increased, the biological effectiveness of the ion beams decreased due to the heterogeneity. The reduction in biological effectiveness was pronounced for lighter H- and He-ion beams compared to heavier C-, O-, and Ne-ion beams. The RBE-weighted dose in the target for HSG (CHO) cells decreased by 41.2% (44.3%) for the H-ion beam, while it decreased by 16.7% (14.7%) for the Ne-ion beam at a prescribed dose of 15 Gy under a of 2.5 mmHg. Significance. The intra-tumoral cellular heterogeneity causes a significant reduction in biological effectiveness of ion beams. These effects should be considered in estimation of therapeutic outcomes.