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Bailat, C.

Publications and source records attributed to Bailat, C..

2 recordsLinked to original sources

Dosimetric and biologic intercomparison between electron and proton FLASH beams

Background and purposeThe FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at a mean dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by e vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methodsThe electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH ([≥]100 Gy/s eFLASH and pFLASH) irradiation. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed with previously validated models. ResultsDoses measured at Gantry1 were in agreement ({+/-} 2.5%) with reference dosimeters calibrated at CHUV/IRA. The neurocognitive capacity of e and pFLASH irradiated mice was indistinguishable from the control while both e and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained with the two beams and was similar between e and pFLASH vs. e and pCONV. Tumor rejection was similar indicating that T-cell memory response is beam-type and dose-rate independent. ConclusionDespite major differences in the temporal microstructure, this study shows that dosimetric standards can be established. The sparing of brain function and tumor control produced by the two beams were similar, suggesting that the most important physical parameter driving the FLASH effect is the overall time of exposure which should be in the range of hundreds of milliseconds for WBI in mice. In addition, we observed that immunological memory response is similar between electron and proton beams and is independent off the dose rate.

cancer biology↗

Hypoxic tumors are sensitive to FLASH radiotherapy

Tumor hypoxia is a major cause of resistance to cancer treatments and especially to radiotherapy (RT) and we wanted to assess whether ultra-high dose rate FLASH RT could overcome this resistance. We engrafted tumor cells of various origins subcutaneously in mice to provide a reliable and rigorous way to modulate oxygen supply via vascular clamping or carbogen breathing. We irradiated tumors using a single 20 Gy fraction at either conventional (CONV) or FLASH dose-rate. Using multiple different subcutaneous tumor models, and in contrast CONV-RT, FLASH-RT retained anti-tumor efficacy under extreme hypoxia. These findings demonstrate that in addition to normal tissue sparing, FLASH-RT overcomes hypoxia-mediated tumor resistance. Follow-up molecular analysis using RNAseq profiling uncovered FLASH-specific inhibition of cell proliferation and translation as well as metabolic shifts that discriminated FLASH-RT from CONV-RT. These data provide new and specific insights into the mechanism of action and identify novel targets for intervention.

cancer biology↗