Title:
The dependence of optimal fractionation schemes on the spatial dose distribution.

Abstract:
We consider the fractionation problem in radiation therapy. Tumor sites in which the dose-limiting organ at risk (OAR) receives a substantially lower dose than the tumor, bear potential for hypofractionation even if the α/β-ratio of the tumor is larger than the α/β-ratio of the OAR. In this work, we analyze the interdependence of the optimal fractionation scheme and the spatial dose distribution in the OAR. In particular, we derive a criterion under which a hypofractionation regimen is indicated for both a parallel and a serial OAR. The approach is based on the concept of the biologically effective dose (BED). For a hypothetical homogeneously irradiated OAR, it has been shown that hypofractionation is suggested by the BED model if the α/β-ratio of the OAR is larger than α/β-ratio of the tumor times the sparing factor, i.e. the ratio of the dose received by the tumor and the OAR. In this work, we generalize this result to inhomogeneous dose distributions in the OAR. For a parallel OAR, we determine the optimal fractionation scheme by minimizing the integral BED in the OAR for a fixed BED in the tumor. For a serial structure, we minimize the maximum BED in the OAR. This leads to analytical expressions for an effective sparing factor for the OAR, which provides a criterion for hypofractionation. The implications of the model are discussed for lung tumor treatments. It is shown that the model supports hypofractionation for small tumors treated with rotation therapy, i.e. highly conformal techniques where a large volume of lung tissue is exposed to low but nonzero dose. For larger tumors, the model suggests hyperfractionation. We further discuss several non-intuitive interdependencies between optimal fractionation and the spatial dose distribution. For instance, lowering the dose in the lung via proton therapy does not necessarily provide a biological rationale for hypofractionation.