Comparison of continuous and pulsed low dose rate brachytherapy: Biological equivalence in vivo

Purpose: Recent studies of human cell lines cultured in vitro and mathematical modeling of the response of acute and late responding tissues have predicted conditions for the equivalence in terms of cell killing of continuous and pulsed dose rate brachytherapy. The aim of this study was to test these predictions in vivo using an acutely responding normal tissue. Methods and Materials: The microcolony assay was used to quantify the survival of jejunal stem cells in vivo. Mice were exposed to graded doses of ⁶⁰Co delivered continuously or as 1- or 10-min pulses given once-per-hour at an average dose rate of 0.7 Gy/hr. In both cases the total dose-per-hour was 0.7 Gy. Overall exposure times ranged between about 30 and 60 h. Mice were sacrificed 3.5 days after exposure, the bowel removed for routine histological preparation, and number of surviving crypts quantified microscopically. Results: An average dose-per-hour of 0.7 Gy, a pulse width of 10 min, and a pulse frequency of 1 h resulted in biological equivalence of pulsed to continuous treatment. Delivering the pulse in a period of 1 min at a dose rate 10-fold higher resulted in a modest 3-4% shift in the survival curve to lower isoeffective doses. The slopes of the survival curves as described by D_O values were similar for all treatment regimens tested. Conclusion: This in vivo study validates the prediction of biological equivalence between pulsed and continuous brachytherapy at a clinically relevant average dose rate and may generate further interest in this new treatment modality because of its advantages in radiation protection, dose optimization, and cost relative to standard low dose rate brachytherapy techniques.