Biology subjects

Bailat, C.

Publications and source records attributed to Bailat, C..

3 recordsLinked to original sources

bioRxiv2025

Decrease in dose per fraction impairs the FLASH sparing effect in murine intestine model

PurposeFLASH radiotherapy (FLASH) can ease radiation-induced normal tissue toxicities; however, its benefit in clinically relevant fractionation protocols remains insufficiently explored. This study investigated the FLASH sparing effect under two fractionated regimens using a murine model of acute gastrointestinal toxicity. Methods and MaterialsTumor-free C57BL/6 mice received abdominal irradiation with either conventional radiotherapy (CONV) or FLASH using a 9 MeV electron beam. Three dose delivery protocols were assessed: single-fraction delivery, two equal fractions over two consecutive days, and ten equal daily fractions over two weeks. Dose escalation was performed within each protocol, while overall survival was used to monitor normal tissue sparing. The FLASH dose modifying factor (FDMF) was derived from normal tissue toxicity probability (NTCP) curves to quantify the relative protective effect of FLASH. ResultsThe single-fraction irradiation demonstrated a significant FLASH sparing effect, with an FDMF of 1.14. In contrast, this protective effect was diminished in the fractionated protocols, with the two-fraction regimen yielding an FDMF of 1.03, while the ten-fraction regimen showed no measurable sparing (FDMF = 1.00). ConclusionsIn an acute responding model of radiation-induced abdominal toxicity, the FLASH sparing effect was substantially reduced with a two-fraction regimen and completely absent with a ten-fraction regimen. These findings suggest that the benefit of FLASH may be limited at lower doses per fraction and highlight the need for further studies in other clinically relevant models to better define the boundaries of its therapeutic applicability. HighlightsO_LIFLASH-RT spares mice intestine from acute toxicity for single-dose delivery. C_LIO_LIFLASH effect declines in mice intestine with more fractions and less dose/fraction. C_LIO_LIFLASH sparing in mice intestine is lost with ten equal fractions over two weeks. C_LI

cancer biology↗

bioRxiv2023

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↗

bioRxiv2022

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↗