Better efficacy of synchrotron spatially micro-fractionated radiotherapy than uniform radiotherapy on glioma
Menée à l'aide d'un modèle murin de gliome, cette étude montre qu'une radiothérapie synchrotron par microfaisceaux est, du point de vue du contrôle de la croissance tumorale et de la survie, plus efficace qu'une radiothérapie synchrotron à larges faisceaux
Purpose : Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred Gray. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial location. But mechanisms responsible for such property are not fully understood. Methods : Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam radiation therapy (BB) delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. Results : MRT significantly improved survival of rats bearing 9L intracranial glioma compared to BB delivered at a comparable dose (p<0.001); the efficacy of MRT and BB was similar when the MRT-dose was half that of BB. The greater efficacy of MRT is not correlated with a difference in cell proliferation (Mki67 and PCNA) or in transcriptomic stimulation of angiogenesis (VEGF-A or Tie2) but with a higher cell death rate (Fas) and higher recruitment of macrophages (Tie1 and CD68 transcripts) few days after MRT. Conclusions : These results demonstrate the superiority of MRT over BB when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cells activation in brain tumors treated by MRT may be involved in such responses.