Abstract A002: Flash proton re-irradiation and hypofractionation alleviate radiation-induced toxicity of the head and neck tissues in mice

Abstract

The effect of FLASH Proton Radiation therapy (F-PRT) in decreasing normal tissue toxicity while maintaining equal tumor control compared to Standard Proton Radiation therapy (S-PRT) has been previously investigated for head and neck tissues in mice using a single dose of either S-PRT/F-PRT. Here, we studied the effect of F-PRT following a hypo-fractionated regimen and in a re-irradiation setting. The head and neck area of C57Bl/6 mice was irradiated with a single dose of 12 Gy of F-PRT (128Gy/s) or S-PRT (0.95 Gy/s) and was followed with a hypo-fractionated re-irradiation scheme (6 Gy x 3). Mice with orthotopic tongue tumors were also irradiated with two different hypo-fractionated regimes of 8 Gy x 3 and 9 Gy x 3 respectively. Compared to the re-irradiation with S-PRT, F-PRT re-irradiated mice mitigate xerostomia by improving salivary flow. Histopathological analysis of the salivary gland showed increased acinar cell atrophy and individual cell death in the submandibular gland in mice re-irradiated with S-PRT compared to the ones re-irradiated with F-PRT. Re-irradiation with hypo-fractionated S-PRT showed a significant increase in the alveolar bone loss compared to F-PRT. Following irradiation with hypo-fractionated F-PRT mice with orthotopic tongue tumors significantly increases the overall survival compared to the ones irradiated with hypo-fractionated S-PRT. This study provides evidence of the sparing effect of F-PRT in minimizing radiation-induced head and neck tissue toxicity in a hypo-fractionated re-irradiation setting. The results support the efficacy of F-PRT for clinical application.

Citation Format: Priyanka Chowdhury, George Morcos, Michele Kim, Yuewei Lin, Ling Qin, James Metz, Alexander Lin, Costas Koumenis. Flash proton re-irradiation and hypofractionation alleviate radiation-induced toxicity of the head and neck tissues in mice. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A002.