From conventional dose-rate to FLASH radiotherapy
Lectio magistralis by Vincent Favaudon, Institut Curie
The radiation dose-rate is the most versatile and badly controlled factor in radiotherapy and research in radiobiology.
From brachytherapy to external beam radiotherapy, most current facilities deliver electrons, photons or protonsat dose-rates between 0.001 and 0.40 Gy/s.
Eight years ago ultrahigh dose-rate irradiation (UHDR, intra-pulse dose-rate ≥ 105 Gy/s) unexpectedly demonstrated dramatic sparing of mouse lung from radio-induced fibrosis without modification of the antitumor efficiency.
This disruptive concept, known as the FLASH effect, has been confirmed in all mouse organs tested so far as well in higher mammals and in a patient treated for surface-seated tumors.
Together with the recent expansion of stereotactic radiotherapy without flattening filter, FLASH appeals to reconsider the biological impact of the dose rate and return back to the source, i. e., to analysis of the intimate mechanisms of radio-induced free radical reactions.
In this lecture he shall present some molecular aspects of time-dependent biological responses with attention to cell cycle progression, split-dose recovery, chromatin remodeling at sites of DNA damage, and finally oxylipins in the context of the FLASH effect.