Dose to water versus dose to medium from cavity theory applied to small animal irradiation with kilovolt x-rays

Dose reporting is a matter of concern in the preclinical field as the different dose descriptors dose-to-water-in-medium (D-wm) and dose-to-medium-in-medium (D-mm) coexist. For kV photons differences between both quantities are expected to be amplified due to photon energy absorption coefficients differences for different media, and could represent a limiting factor for accurate translation of pre-clinical research into clinical trials. The main goal of this study was to analyse the relationship between D-mm and D-wm for kV irradiation of small animals, using different flavours of the intermediate cavity theory (ICT).

Irradiations of mathematical phantoms and a mouse CT scan, both with different voxel sizes and materials, were investigated. A modified version of the Monte Carlo code DOSXYZnrc was used to derive D-mm and convert to D-wm using ICT. Local photon spectra were generated in different regions of the mouse.

Depending on energy and cavity size, which we equate to the voxel size, D-mm ranged from 0.68 to 4.37 times D-wm. Higher kV energy combined with very small cavity sizes yielded decreased D-mm in comparison to D-wm; this behaviour was reversed for larger cavities combined with lower kV energies. Hence, the impact of the cavity dimensions on estimated D-wm is significant on pre-clinical kV beams. Dmm and D-wm in the ex vivo male mouse were found to differ by -29% to 286%. Caution is advised when using the ICT due to a lack of consensus on weighting factor (d-parameter) deriving methods; for the same irradiation conditions, different d-values affected D-wm up to 20%. Pre-clinically, such divergence between dose descriptors could enable biological damage.

The abiding debate over which quantity to favour is foreseen to linger while it is unclear which quantity correlates better with the biological effects of ionizing irradiation: preclinical radiotherapy might represent an ideal platform for measurement-based studies to settle this fundamental question. Finally, dose distribution comparisons require caution and should use the same reporting quantity.