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

Objective.The tumor microenvironment characterized by heterogeneously organized vasculatures causes intra-tumoral heterogeneity of oxygen partial pressurepat the cellular level, which cannot be measured by current imaging techniques. The intra-tumoral cellularpheterogeneity 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 cellularpdistributions were simulated with a numerical tumor model for average oxygen pressuresp¯tranging 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 constantp¯tvalues. Radiosensitivities of human salivary gland tumor (HSG) and Chinese hamster ovary (CHO) cells were investigated. The planned dose distributions were then recalculated by taking thepheterogeneity into account.Main results.Asp¯tdecreased and prescribed dose increased, the biological effectiveness of the ion beams decreased due to thepheterogeneity. 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 ap¯tof 2.5 mmHg.Significance.The intra-tumoral cellularpheterogeneity causes a significant reduction in biological effectiveness of ion beams. These effects should be considered in estimation of therapeutic outcomes.