Ultra-High Dose Rate FLASH Effect on Head and Neck Cancer Cells and Normal Salivary Gland in Mice

Abstract

<h3>Purpose/Objective(s)</h3> Ultra-high dose rate irradiation (FLASH) is a novel therapeutic modality that has been reported to spare tissues compared to conventional dose rate. We aimed to investigate the effect of FLASH on head and neck (H&N) cancer cells and salivary gland dysfunction caused by radiotherapy. <h3>Materials/Methods</h3> H&N cancer cells (HSG and FaDu) were irradiated with 10 MeV electron beam at a dose rate of 132.2Gy/s (FLASH) or 0.1Gy/s (CONV), by a modified clinic linear accelerator. The irradiated dose was confirmed with EBT-XD film, and 3, 7, and 11 Gy were irradiated. We evaluated the cell cycle and the surviving fraction of cells with clonogenic assays. We administered single dose head and neck irradiation to mice with a 6 MeV electron beam at dose rate of 105.6-126 Gy/s (FLASH) or 0.03Gy/s (CONV), using a modified linear accelerator. The irradiated dose was confirmed with EBT3 film, and 9-76 Gy and 10-30 Gy were irradiated for FLASH and CONV, respectively. Parotid and submandibular glands were obtained from mice at 3 and 30 days after irradiation. Immunohistological examination and apoptotic assays were conducted to assess the radiation response. <h3>Results</h3> The proportion of sub G0/G1 was higher in the FLASH group, and the surviving fraction was significantly decreased in FLASH through every dose range. At three days post-irradiation, both 10 Gy and 30 Gy irradiated groups showed a greater number of salivary cells and increased expression of AQP5 in FLASH compared to conventional irradiated mice. As a late toxicity (30 days of irradiation), fibrosis did not show any significant difference, although FLASH group received much higher radiation dose. There was no difference in apoptosis between groups on post 3 days, but FLASH showed significantly less degree of apoptosis on 30 days after irradiation. <h3>Conclusion</h3> This study demonstrates that FLASH irradiation strengthens the therapeutic effect for H&N cancers and attenuates radiation-induced salivary gland damage. Further research is needed on the biological mechanisms involved.