Effect of patient variation on standard- and hypo-fractionated radiotherapy of prostate cancer

Recent publications suggested that the α/β ratio in the well-known linear quadratic (LQ) model could be as low as 1.5 Gy for prostate cancer, indicating that prostate cancer control might be very sensitive to changes in the dose fractionation scheme. This also suggests that the standard-fractionation scheme based on large α/β ratios may not be optimal for the radio-therapeutic management of prostate cancer. Hypo-fractionated radiotherapy for prostate cancer has received more attention recently as an alternative treatment strategy, which may lead to reduced treatment time and cost. However, hypofractionated radiotherapy may be more sensitive to patient variation in terms of disease control than standard-fractionated radiotherapy. The variation of LQ parameters a and β for a patient population may compromise the outcome of the treatment. This effect can be studied by the introduction of the σ_α and σ_β parameters, which are the standard deviations of Gaussian distributions around α₀ and β₀. The purpose of this study is to examine the effect of patient variation in a and β on tumour control probability for standard- and hypo-fractionated radiotherapy of prostate cancer. The tumour control probability based on the LQ model is calculated using parameters α, β, σ_α and σ_β. Our results show that σ_α is an important parameter for radiotherapy fractionation, independent of the α/β ratio. A large σ_αwill result in a significant increase in the radiation dose required to achieve the same 95% TCP. Compared with the standard-fractionated scheme, σ_α has a smaller effect on hypo-fractionated treatment at lower α/β ratios. On the other hand, for lower α/β ratios, the β term also plays a more important role in cell-killing and therefore the patient variation parameter σ_β must be considered when designing a new dose fractionation scheme.