[Biologic effects of high doses per fraction].

The radiobiological concepts described for conventional doses per fraction (1.8 to 2Gy) seem difficult to translate to high doses per fraction radiobiology. In fact, specific mechanisms are involved during high dose per fraction irradiation, involving vascular microenvironment damage and anti tumor immune response. The "5R's" of "classical" radiobiology (factors influencing the response of healthy or cancer cells to irradiation) seem to play a less important role in case of high doses per fraction. In addition, applicability of the linear quadratic model in this context is debated. It is therefore difficult to obtain reliable equivalent doses, hence the importance of including our patients in clinical trials, especially in case of concomitant systemic treatments. In addition to stereotactic radiotherapy, flash irradiations defined by a dose rate approximately 2000 times faster than "conventional" irradiation can also deliver high doses per fraction, with a much better tolerance for normal tissue without loss of anti tumor efficacy. Finally, availability of robust prospective data is a prerequisite to answer the question of short and long-term risk/benefit ratio of these different irradiation techniques.