Constraints in the use of repair half times and mathematical modelling for the clinical application of HDR and PDR treatment schedules as an alternative for LDR brachytherapy

Abstract

Using theoretical models based on radiobiological principles for the design of new treatment schedules for HDR and PDR brachytherapy, it is important to realise the impact of assumptions regarding the kinetics of repair. Extrapolations based on longer repair half times in a continuous LDR reference scheme may lead to the calculation of dangerously high doses for alternative HDR and PDR treatment schedules. We used the clinical experience obtained with conventional ERT and LDR brachytherapy in head and neck cancer as a clinical guideline to check the impact of the radiobiological parameters used. Biologically equivalent dose (BED) values for the in clinical practice of LDR brachytherapy recommended dose of 65-70 Gy (prescribed at a dose rate between 30-50 cGy/h) are calculated as a function of the repair half time. These BED values are compared with the biological effect of a clinical reference dose of conventional ERT with 2 Gy/day and complete repair between the fractions. From this comparison of LDR and ERT treatment schedules, a range of values for the repair half times of acute or late responding tissues is demarcated with a reasonable fit to the clinical data. For the acute effects (or tumor control) the best fits are obtained for repair half times of about 0.5 h, while for late effects the repair half times are at least 1 h and can be as high as 3 h. Within these ranges of repair half times for acute and late effects, the outcome of'alternative5 HDR or PDR treatment schedules are discussed. It is predominant ly the late reacting normal tissue with the longer repair half time for which problems will be encountered and no or only marginal gain is to be expected of decreasing the dose rate per pulse in PDR brachytherapy.

Role of Interstitial PDR Brachytherapy in the Treatment of Oral and Oropharyngeal Cancer

“…Radiobiological studies showed, that PDR brachytherapy is probably equivalent to LDR brachytherapy models [1,5,7,10,12,13,17,19,24,29,32,42]. Initial clinical data for different clinical situations provided some evidence to support this hypothesis [8,9,11,15,18,21,26,30,31,34,36,37,39,40,43].…”

Is pulsed dose rate more damaging to spinal cord of rats than continuous low dose rate?

“…5. There were two components of repair present, including a substantial component of repair shorter than 0J5-0.5 h, in the spinal cord of these ratsl Several other pub lications have demonstrated biexponential repair with both a short and long T 1/2 in the spinal cord of rats [1,22,25,26,28,29,32]. These include one set of experi ments from our group using the same strain of rats and the same HDR irradiation set-up as in the present experiments [22].…”

Pulse Frequency in Pulsed Brachytherapy Based on Tissue Repair Kinetics

“…The dissociation of acute effects and tumor control from late effects suggest shorter T 1/2 for early-responding normal tissue and tumor than for late-responding normal tissue (30). A range of estimated values for tissue repair half-times that were derived by fitting clinical data of CLDR brachytherapy and conventional external-beam radiotherapy has been described recently (20). For tumor and early-responding normal tissue, T 1/2 most probably lies between 0.2 and 1 h and, for late effects, between 1 and 3 h.…”

“…Cell proliferation was not taken into account because the overall treatment time was restricted to a maximum of 40 h. The time for delivery of 1 Gy was assumed to be 0.075 h (i.e., for a total dose of e.g., 20 Gy, the product of N and T pulse was fixed at 1.5 h). The biological parameters ␣/␤ and T 1/2 and the physical parameters CLDR dose rate, number of pulses, period time, and total dose used in radiobiological modeling are presented in Table 2.…”