Is α/β for breast cancer really low?

Purpose: Low α/β ratio for breast cancer has drawn a growing interest for exploring hypofractionation for breast irradiation. This work is to confirm the low α/β ratio based on large randomized clinical trials of breast irradiation. Methods and materials: A model based on the generalized linear-quadratic (LQ) model and Poisson statistical model was developed to calculate disease-free survival with consideration of clonogen proliferation during the course of radiation treatment and exponential behavior of survival rate with follow-up time. Outcome data from a series of randomized clinical trials of early-stage breast radiotherapy were fitted to estimate the model parameters. Other clinical outcomes, including treatments with surgery alone or radiotherapy alone were used to validate the model and the estimated parameters. Hypofractionation regimens were proposed based on the newly estimated LQ parameters. Results: Plausible population averaged radiobiologic parameters for breast cancer (95% confidence level) are α/β = 2.88 (0.75-5.01) Gy; α = 0.08 ± 0.02 Gy-1; potential doubling time Td = 14.4 ± 7.8 day. The analysis of the radiation-alone data suggested an α/β ratio of 3.89 ± 6.25 Gy, verifying the low α/β ratio based on the post-lumpectomy irradiation data. The hypofractionation regimens that are equivalent to the conventional regimen of 2.0 Gy x 25 in 5 weeks include 2.26 Gy x 20, 3.34 Gy x 10, 4.93 Gy x 5 or 3.39 Gy x 10 (BID). Conclusions: The analysis of the available clinical data from multiple institutions support that breast cancer has a low ratio of α/β, encouraging hypofractionated radiotherapy regimens for breast cancer.