PULSED DOSE-RATE AND FRACTIONATED HIGH-DOSE-RATE BRACHYTHERAPY - CHOICE OF BRACHYTHERAPY SCHEDULES TO REPLACE LOW-DOSE RATE TREATMENTS

Purpose: Pulsed dose rate (PDR) brachytherapy is a new type of afterlo ading brachytherapy (BT) in which a continuous low dose rate (LDR) tre atment is simulated by a series of ''pulses,'' i.e., fractions of shor t duration (less than 0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel den Heed Cancer Center, the term ''PDR brachytherapy'' is used for treatment schedules with a large number of fractions (at least four per day), while the term ''fractionated high dose rate (HDR) brachytherapy'' is used for treatment schedules with just one or two brachytherapy fractions per day. Both treatments can b e applied as alternatives for LDR BT. This article deals with the choi ce between PDR and fractionated HDR schedules and proposes possible fr actionation schedules. Methods and Materials: To calculate HDR and PDR fractionation schedules with the intention of being equivalent to LDR BT, the linear-quadratic (LQ) model has been used in an incomplete re pair formulation as given by Brenner and Hall, and by Thames. In contr ast to earlier applications of this model, both the total physical dos e and the overall time were not kept identical for LDR and HDR/PDR sch edules. A range of possible PDR treatment schedules is presented, both for booster applications (in combination with external radiotherapy ( ERT) and for BT applications as a single treatment. Because the knowle dge of both alpha/beta values and the half time for repair of subletha l damage (T-1/2), which are required for these calculations, is quite limited, calculations regarding the equivalence of LDR and PDR treatme nts have been performed for a wide range of values of alpha/beta and T -1/2. The results are presented graphically as PDR/LDR dose ratios and as ratios of the PDR/LDR tumor control probabilities. Results: If the condition that total physical dose and overall time of a PDR treatmen t must be exactly identical to the values for the corresponding LDR tr eatment regimen is not applied, there appears to be less need for stro ng fractionation in PDR schedules. If the overall time is at least as long as that of the LDR schedule and if the total physical dose is (sl ightly) adapted, PDR schedules can be designed using longer pulse inte rvals of up to 3 h. Schedules with sufficiently long intervals have si gnificant logistic advantages in terms of patient care and treatment t olerance. However, in general, PDR schedules that apply more fractiona tion have a lower risk of overdosing normal tissues in comparison to f ractionated HDR schedules. Applying probable ranges for the values of alpha/beta and T-1/2, the model calculations indicate that the differe nces in effects between the proposed fractionated HDR and PDR schedule s could be rather small. To detect the magnitude of these differences, (randomized) clinical studies with rather large patient groups might be needed. Conclusions: Pulsed dose rate treatment schedules with long er intervals of up to 3 h appear adequate to replace LDR treatment sch edules. Whether PDR schedules can, indeed, replace LDR treatment sched ules and whether they offer detectable advantages over schedules with less fractionation (fractionated HDR) should be tested in clinical stu dies.