Spontaneous radiation-induced rib fractures in breast cancer patients treated with postmastectomy irradiation. A clinical radiobiological analysis of the influence of fraction size and dose-response relationships on late bone damage.

The influence of fraction size on normal tissue damage was analysed in 231 patients treated with postmastectomy irradiation given either with a 12-fraction regimen (1978-1980) or with a 22-fraction regimen (1981). Chest radiographs taken 1-6 years after treatment were reviewed for spontaneous, radiation-induced rib fracture within the treated area. Patients treated with a large dose per fraction had significantly higher incidence of late bone damage (19%) than patients treated with a standard dose per fraction (6%) even though they had been treated with the aim to obtain equivalent biologic response according to the NSD formula. Furthermore, there was a clear dose-response relationship, especially in the 12-fraction regimen, where the total dose at the reference point varied over a wide range. Isoeffect doses could be estimated for the two different fractionation schedules. Using the linear quadratic model, alpha/beta ratios for late bone damage were estimated to be within the range of 1.8-2.8 Gy, i.e. similar to those reported for other late responding normal tissues.