Pulsed dose rate brachytherapy.

Pulsed dose rate (PDR) is a new modality for dose delivery in brachytherapy. It uses modern afterloading technology (miniaturized source, cable driven, software controlled), with source activities in the range of 1 Ci, which is actually one tenth of the normal activity used for high dose rate (HDR) brachytherapy. Modern technology allows dose optimization, and source strength in the above-mentioned range creates a new dose rate condition. For small fractions (pulses) with short interpulse intervals, PDR mimics the radiobiology of high dose rate brachytherapy, whereas for bigger doses per fraction, dose adjustments are needed to compensate for the loss of therapeutic ratio. Clinical series showed good figures for local control and toxicity. Almost every clinical site has been reported to have been treated with PDR, with some thousand of patients having been reported. Technical difficulties in some body sites can be overcome by slightly modifying the implant technique. PDR brachytherapy is an ideal environment for the development of new dose fractionation schedules. It creates unique conditions in which to operate. Knowledge of tissue repair kinetics is extremely important for adequate selection of dose per pulse and interpulse interval. Therapeutic ratio can be improved by adjusting interpulse intervals to the repair half-times for normal tissues. On the other hand, superfractionated schedules with low dose per pulse can be explored in conditions of tumor hypoxia, thanks to the predicted hypersensitivity at low dose per fraction. The use of chemical agents (nicotinamide and others) in concomitance with this superfractionated schedules is foreseen in controlled clinical trials. In conclusion, PDR brachytherapy can be considered a new paradigm for dose delivery. It is safe and reliable, can be used in the setting of image-guided radiation therapy, and exploit the differential effect of ionizing radiations by a thorough knowledge of tissue kinetics for an improved therapeutic ratio.