The influence of the number of fractions and bi-exponential repair kinetics on biological equivalence in pulsed brachytherapy.

A linear-quadratic radiobiological model incorporating single or bi-exponential repair kinetics has been used to show the following and other features when a continuous low dose rate (CLDR) 70 Gy/140 h brachytherapy protocol is replaced by a radiobiologically equivalent pulsed dose rate (PDR) system using 140 fractions for reasons of dosage homogeneity. (1) For equivalent effects in late-reacting tissues, the PDR dose (at 5 or 0.05 Gy min-1) x 1 h intervals needs to be reduced by up to only 3%. Progressively further reductions in dose are required when fewer larger fractions are used. (2) When equivalence using pulsed doses is achieved for one normal tissue type, and extrapolated response doses (ERD) are calculated for other tissue types in the irradiated volume, values of the ERD remain within 5% of each other using the above PDR protocol and associated parameters. (3) For tumours with alpha/beta = 10 Gy and a single repair halftime of 0.1-1.0 h, there is no significant loss of therapeutic benefit using the PDR protocol equivalenced for late normal tissue reactions. The strategy of replacing an LDR boost protocol of about 24 Gy by a PDR protocol gives similar levels to the 70 Gy PDR protocol for the expected percentage increase in the biological dose to normal tissues (due to the PDR protocol alone). These calculations also highlight the importance of the values assumed for the conventional alpha/beta ratio and the repair kinetics when estimating equivalent PDR protocols. The use of an inappropriate radiobiological parameterization will lead to erroneous conclusions with the potential to advocate PDR protocols which will, in practice, lead to an increase in late complications.