Abstract PL-3: Breast Radiotherapy: Fractionation and Other Fashions

Abstract Hypofractionation, defined as the use of fraction sizes >2.0 Gy, requires a reduction in the total dose delivered in 1.8–2.0 Gy fractions that takes account of the greater effect per Gy of larger fractional doses. Generations of radiation oncologists have been taught that small (≤2.0 Gy) daily fractions are always gentler on the dose-limiting healthy tissues than on the cancer, thereby optimising clinical benefit. This relationship applies at many tumour sites, but breast cancer is different. Well-designed randomised trials involving >7000 women confirm that there are no advantages to using ≤2.0 Gy fractions, which spare breast cancer as much as the normal tissues. The limits of hypofractionation for whole breast/chest wall radiotherapy are under evaluation in the UK FAST Forward trial, testing 2 dose levels of a 5-fraction regimen given in 1 week against the 3-week UK standard. Hypofractionation can also be employed to match dose intensity more effectively to the spatial pattern of tumour relapse by modulating fraction size across the breast in preference to fraction number, an approach under test in the UK IMPORT HIGH trial. In marked contrast to conservative attitudes towards whole breast hypofractionation, there has been a dash to accelerated hypofractionation schedules among practitioners of partial breast radiotherapy. The mean fractionation sensitivity of breast cancer, expressed as an α/β value, is approximately 3 Gy. The distribution around this point estimate could be wide or narrow; we don't know. The fractionation sensitivities of early responding normal tissues and cancers are postulated to reflect the responses of a limited number of target stem cell populations. Late-responding normal tissues are more complex in that multiple parenchymal and stromal cell lineages and interactions need to be considered. Despite potential complexity, a strong association between the proliferative indices of normal tissue parenchymal cells and fractionation sensitivity support the notion that the latter has a cellular basis, justifying a focus on classical cellular recovery and DNA double strand break (DSB) repair. Differences between healthy and malignant tissues in how they handle DSB are but one of several potential modulators of fractionation sensitivity. The processes are likely to be strongly affected by mutational and epigenetic alternations in tumours, but they foretell a future when predictive biomarkers replace historical dogma in determining fractionation regimens for cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PL-3.