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内容記述 |
[Purpose] The tumor microenvironment characterized by heterogeneously organized vasculatures causes intra-tumoral heterogeneity of oxygen partial pressure <I>p</I> at the cellular level, which cannot be measured by current imaging techniques with a millimeter scale resolution. The intra-tumoral cellular <I>p</I> heterogeneity may lead to a reduction of therapeutic effects of radiation. The purpose of this study was to investigate the effects of the intra-tumoral cellular <I>p</I> heterogeneity on biological effectiveness of H-, He-, C-, O-, and Ne-ion beams for different oxygenation levels, prescribed dose levels, and cancer cell types.[Methods] The intra-tumoral cellular <I>p</I> distributions were simulated with a numerical tumor model for average oxygen pressures <I>p</I><SUB>t</SUB> 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 by assuming uniform <I>p</I> distributions over the target volume at values of <I>p</I><SUB>t</SUB>. Radioresponses of human salivary gland tumor (HSG) and Chinese hamster ovary (CHO) cells were investigated. The planned dose distributions were then recalculated by taking the intra-tumoral cellular <I>p</I> heterogeneity into account.[Results] As prescribed dose increased and <I>p</I><SUB>t</SUB> decreased, the biological effectiveness of the ion beams decreased due to the intra-tumoral cellular <I>p</I> heterogeneity. The reduction in biological effectiveness was pronounced for lighter 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 <I>p</I><SUB>t</SUB> of 2.5 mmHg.[Conclusion] The intra-tumoral cellular <I>p</I> heterogeneity leads to a reduction of therapeutic effects of radiations, regardless of the cancer cell type. The reduction in biological effectiveness was pronounced for lighter ion beams with lower LET, lower oxygenation levels, and higher prescribed doses. The effects of the heterogeneity should be considered when the biological effectiveness of radiations is evaluated based on the 3D-map of the <I>p</I> distribution averaged over the millimeter scale. |
