Spatial Fractionation in Tumor Radiotherapy and Discussed Mechanisms of the Therapeutic Window Extension

Abstract

Irradiation of the tumor through the ridge filters in order to reduce the damage of the normal tissues while maintaining the same damage to the neoplastic tissue as with uniform field is used for many decades. In recent years, a positive effect has been demonstrated using synchrotron radiation and beams of accelerated protons with radiation fields diminished to 25-100 micrometers with the same distances between them. Less skin damage achieved while maintaining the required level of large neoplasms eradication in the case of X-ray and gamma irradiation through ridge filters can be partially explained by the features of the physical distribution of the dose over the depth of the irradiated tissue, namely, the “merging” of fields at depth. But the good results from the use of the ‘hills and valleys’ in radiation fields created by the modern radiation sources have attracted attention to radiobiological issues for explaining the principal differences in reaction to spatial fractionation of the absorbed dose between tumor and normal tissues. We are talking about the role of the so-called ‘communal effect/bystander effect’, the effect of radiation on the immunological processes, the differences in damage and restoration of the microvasculature in normal and tumor tissue, etc. Although there is the lot of publications concerning experimental studies of the effectiveness of ‘spatial dose fractionation’, as well as those considering radiobiological mechanisms of the observed expansion of the ‘therapeutic interval’, there is still no clarity in this issue. The purpose of this review is to systematize the available data on the clinical and experimental confirmation of the effectiveness of ‘spatial fractionation’ and the various explanations of its advantages over conventional, uniform dose distribution. Special attention is paid to the issues of combination of spatial fractionation with superhigh dose rate irradiation (FLASH-radiotherapy) on the new radiation facilities, including proton accelerators, which are now in use in this country.