Break-even dose level for hypofractionated treatment schedules

Purpose To derive the isodose line R relative to the prescription dose below which irradiated normal tissue (NT) regions benefit from a hypofractionated schedule with an isoeffective dose to the tumor. To apply the formalism to clinical case examples. Methods From the standard biologically effective dose (BED) equation based on the linear-quadratic (LQ) model, the BED of an NT that receives a relative proportion r of the prescribed dose per fraction for a given alpha/beta-ratio of the tumor, (alpha/beta)(T), and NT, (alpha/beta)(NT), is derived for different treatment schedules while keeping the BED to the tumor constant. Based on this, the break-even isodose line R is then derived. The BED of NT regions that receive doses below R decreases for more hypofractionated treatment schedules, and hence a lower risk for NT injury is predicted in these regions. To assess the impact of a linear behavior of BED for high doses per fraction (>6 Gy), we evaluated BED also using the LQ-linear (LQ-L) model. Results The formalism provides the equations to derive the BED of an NT as function of dose per fraction for an isoeffective dose to the tumor and the corresponding break-even isodose line R. For generic alpha/beta-ratios of (alpha/beta)(T )= 10 Gy and (alpha/beta)(NT )= 3 Gy and homogeneous dose in the target, R is 30%. R is doubling for stereotactic treatments for which tumor control correlates with the maximum dose of 100% instead of the encompassing isodose line of 50%. When using the LQ-L model, the notion of a break-even dose level R remains valid up to about 20 Gy per fraction for generic alpha/beta-ratios and DT=2(alpha/beta). Conclusions The formalism may be used to estimate below which relative isodose line R there will be a differential sparing of NT when increasing hypofractionation. More generally, it allows to assess changes of the therapeutic index for sets of isoeffective treatment schedules at different relative dose levels compared to a reference schedule in a compact manner.

Automated summary

The formalism aims to establish the isodose line R relative to the prescription dose, below which irradiated normal tissue regions benefit from a hypofractionated schedule with an isoeffective dose to the tumor. By using a standard BED equation based on the LQ model, the formalism allows for the calculation of the BED of NT regions receiving varying doses per fraction, leading to the derivation of the break-even isodose line R. The results demonstrate the potential for differential sparing of NT when increasing hypofractionation and provide insights into changes in the therapeutic index for sets of isoeffective treatment schedules.