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.