Radiobiology of brachytherapy: The historical view based on linear quadratic model and perspectives for optimization.

Most preclinical studies examining the radiobiology of brachytherapy have focused on dose rate effects. Scarcer data are available on other major parameters of therapeutic index, such as cell cycle distribution, repopulation or reoxygenation. The linear quadratic model describes the effect of radiotherapy in terms of normal tissue or tumour response. It allows some comparisons between various irradiation schemes. This model should be applied cautiously for brachytherapy, because it relies on cell death analysis only, and therefore partially reflects the biological effects of an irradiation. Moreover, the linear quadratic model validity has not been demonstrated for very high doses per fraction. A more thorough analysis of mechanisms involved in radiation response is required to better understand the true effect of brachytherapy on normal tissue. The modulation of immune response is one promising strategy to be tested with brachytherapy. A translational approach applied to brachytherapy should lead to design trials testing pharmacological agents modulating radiation response, in order to improve not only local control, but also decrease the risk of distant failure. Here we review the radiobiology of brachytherapy, from the historical view based on linear quadratic model to recent perspectives for biological optimization.