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Recent developments in FLASH radiotherapy has raised large interest in the radiation community, particularly for its promises to reduce radiation toxicity on healthy tissue without compromising the anti-tumoral effects of radiotherapy (the so-called FLASH effect). Most preclinical FLASH studies have been performed in mice, zebrafish and non-primate mammals but, while the first trials implementing FLASH radiotherapy in the clinic are ongoing, the effect of FLASH in human is still unknown. Previous results from the lab, using an ex vivo lung organotypic slice model recapitulating the complex lung architecture, have shown that FLASH spares cycling cells in mouse lungs 24 hours after irradiation.  To provide some first clues, we aimed to use this ex vivo lung model to determine the effect of FLASH radiotherapy in the human lung.

First, we collected human healthy lung samples from lobectomies performed at Institut Mutualiste Montsouris (IMM). Lung samples are sliced and irradiated at a dose of 9 Gy either in conventional or FLASH modes with the ElectronFLASH irradiator (SIT). Slices are incubated with EdU and the proportion of EdU+ cycling cells are quantified twenty-four hours after irradiation.

Preliminary analysis from the first patients indicate that a higher proportion of EdU+ cells is present in human lung organotypic slices at twenty-four hours after FLASH compared to conventional irradiation. This result suggests that, in agreement with the data obtained from mouse using the same protocol, FLASH radiotherapy spares the proportion of cycling cells in human lung analyzed ex vivo.

This study provides a first evidence that FLASH radiotherapy can spare healthy human lung tissue. A more comprehensive analysis including a larger cohort of patients is ongoing and the results will be presented in May 2023.