Equivalent Uniform Dose (EUD) and the Evaluation of Cell Survival in Spatially Fractionated Radiotherapy (SFRT)

Abstract

SFRT has shown promise as a treatment modality to decrease normal tissue sparing without compromising tumor coverage, i.e., an increase in the therapeutic window compared to more conventional uniform radiation therapy (RT). The aim of this work is to examine and test several alternative bio-dosimetric parameters for the prediction of cell survival for normal-tissue and tumor cell lines irradiated in vitro with uniform and microbeam radiotherapy (MRT). A bespoke tungsten collimator with 50 parallel, 50 µm wide slits and 400 µm slit spacing was mounted into an x-ray cabinet. Human fibroblast (MRC5) and two human tumor cell lines (LN18 and A549) were irradiated with a range of doses (< 10 Gy) for uniform and MRT (50um slits, 400um center spacing) using kV X-rays. Average, mean and valley dose as useful predictive metrics of cell survival are compared to the equivalent uniform dose (EUD) with biological parameters estimated from uniform-dose experiments. We find that EUD, with linear-quadratic (LQ) model parameters, is more predictive for survival after SFRT than maximum, minimum or average dose. The maximum and average doses are correlated very poorly with in vitro cell survival. The difference in cell survival between uniform and MRT irradiation as a function of EUD is cell-type and dose dependent. The report results suggest that MRT is more effective at cell killing of tumor-cell lines than uniform irradiation for both tumor cell lines. However, MRT is less effective at killing normal tissue cells than uniform irradiation. EUD is a superior predictor of in vitro cell survival than other metrics sometimes used in the SFRT literature, including mean dose, maximum dose, and valley dose. The reported studies provide some evidence that SFRT may increase the therapeutic ratio by producing spatial dose distributions that effectively reduce normal-tissue damage with little or no change in biological damage to tumor cells. Additional studies are needed to further extend and generalize our results and to test our conclusions against a larger dose range, low and high linear energy transfer (LET) radiations and additional cell lines.