Clinical implications of incomplete repair parameters for rat spinal cord:The feasibility of large doses per fraction in PDR and HDR brachytherapy

Purpose: To evaluate the clinical implications of the repair parameters det ermined experimentally in rat spinal cord and to test the feasibility of la rge doses per fraction or pulses in daytime high-dose-rate (HDR) or pulsed- dose-rate (PDR) brachytherapy treatment schedules as an alternative to cont inuous low-dose-rate (CLDR) brachytherapy. Methods and Materials: BED calculations with the incomplete repair LQ-model were performed for a primary CLDR-brachytherapy treatment of 70 Gy in 140 h or a typical boost protocol of 25 Gy in 50 h after 46-Gy conventional ext ernal beam irradiation (ERT) at 2 Gy per fraction each day. Assuming biphas ic repair kinetics and a variable dose rate for the iridium-192- (Ir-192) s tepping source, the LQ-model parameters for rat spinal cord as derived in t hree different experimental studies were used: (a) two repair processes wit h an alpha/beta ratio = 2.47 Gy and repair half-times of 0.2 h (12 min) and 2.2 h (Pop et. al.); (b) two repair processes with an alpha/beta ratio = 2 .0 Gy and repair half-times of 0.7 h (42 min) and 3.8 h (Ang et al.); and ( c) two repair processes with an alpha/beta ratio = 2.0 Gy and repair half-t imes of 0.25 h (15 min) and 6.4 h (Landuyt et al.). For tumor tissue, an al pha/beta ratio of 10 Gy and a monoexponential repair half time of 0.5 h was assumed. The calculated BED values were compared with the biologic effect of a clinical reference dose of conventional ERT with 2 Gy/day and complete repair between the fractions. Subsequently, assuming a two-catheter implan t similar to that used in our experimental study and with the repair parame ters derived in our rat model, BED calculations were performed for alternat ive PDR- and HDR-brachytherapy treatment schedules, in which the irradiatio n was delivered only during daytime. Results: If the repair parameters of the study of Pop et al., Ang et al., o r Landuyt et al. are used, for a CLDR-treatment of 70 Gy in 140 h, the calc ulated BED values were 117, 193, or 216 Gy(sc) (Gy(sc) was used to express the BED value for the spinal cord), respectively. These BED values correspo nd with total doses of conventional ERT of 65, 96, or 104 Gy. The latter tw o are unrealistic high values and illustrate the danger of a straightforwar d comparison of BED values if repair parameters are used in situations quit e different from those in which they were derived. For a brachytherapy boos t protocol, the impact of the different repair parameters is less, due to t he fact that the percentage increase in total BED value by the brachytherap y boost is less than 50%. If a primary treatment with CLDR brachytherapy delivering 70 Gy in 140 h ha s to be replaced, high doses per fraction or pulses (> 1 Gy) during daytime can only be used if the overall treatment time is prolonged with 3-4 days. The dose rate during the fraction or pulse should not exceed 6 Gy/h. For a typical brachytherapy boost protocol after 46 Gy ERT, it seems to be safe to replace CLDR delivering a total dose of 25 Gy in 50 h by a total dose of 24 Gy in 4 days with HDR or PDR brachytherapy during daytime only. Total d ose per day should be limited to 6 Gy, and the largest time interval as pos sible between each fraction or pulse should be used. Conclusion: Extrapolations based on longer repair half-times in a CLDR refe rence scheme may lead to the calculation of unrealistically high BED values and dangerously high doses for alternative HDR and PDR treatment schedules . Based on theoretical calculations with the IR model and using the repair parameters derived in our rat spinal cord model, it is estimated that with certain restrictions, large doses per fraction or pulses can be used during daytime schedules of HDR or PDR brachytherapy as an alternative to CLDR br achytherapy, especially for those treatment conditions in which brachythera py is used after ERT for only less than 50% of the total dose. (C) 2001 Els evier Science Inc.