The normal tissue effects of microbeam radiotherapy: what do we know, and what do we need to know to plan a human clinical trial?

Abstract

Purpose: Microbeam Radiotherapy (MRT) is a promising pre-clinical cancer therapy which represents a radical departure from the radiobiological principles of conventional radiotherapy (CRT). In order to translate MRT to human clinical trials, robust normal tissue toxicity data are required. This review summarizes the normal tissue effects reported by pre-clinical MRT animal studies and compares these data to clinical recommendations in CRT. Conclusion: Few pre-clinical studies are specifically designed to evaluate the dose-response of normal tissue to MRT. However, it remains clear that a range of normal tissues can tolerate peak MRT doses at least an order of magnitude higher than CRT. Furthermore, the dose deposited in the valley regions, predominantly determined by microbeam spacing, has a greater influence on the normal tissue response to MRT compared to the peak regions. The development of a new normal tissue complication probability model for MRT, in conjunction with a treatment planning system, will be pivotal in the collection of robust normal tissue toxicity data and the translation of MRT to clinical use.