| Summary: | Background and purpose: linear quadratic models predict that hypofractionation increases the biological effect of physical dose inhomogeneity. The clinical significance of this effect was tested retrospectively in a trial of adjuvant breast hypofractionation. Methods: the UK FAST trial randomised 915 women after breast conservation surgery between standard fractionation and two dose levels of a 5-fraction regimen delivering 5.7 or 6.0 Gy fractions in 5 weeks, using 3D dosimetry. Logistic regression tested for association between the absolute volumes receiving different isodose level >100% of prescribed dose (hotspots) and the risk of change in 2-year photographic breast appearance. The strength of this association was compared between control and hypofractionated groups. Results: three hundred and ninety datasets from 11 participating centres were available for analysis. At 2 years post-randomisation, 81 (20.8%) had mild change and 24 (6.2%) had marked change in photographic breast appearance. After adjusting for breast size and surgical deficit, there was no statistically significant association between the risk of 2-year change in breast appearance and dose inhomogeneity in either the control or hypofractionated schedules, according to the various definitions of hotspots analysed. The magnitude of the effect of dosimetry on 2-year change in breast appearance did not vary significantly between control and hypofractionated schedules for any of the dosimetry parameters (p > 0.05 for all heterogeneity tests). Conclusion: dose inhomogeneity had no greater impact on the risk of 2-year change in photographic breast appearance after hypofractionated breast radiotherapy than after standard fractionation
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