ETD

• chorioallantoic membrane model
• FLASH radiotherapy
• pancreatic adenocarcinoma
• preclinical radiotherapy models
• therapeutic ratio

FLASH radiotherapy (FLASH-RT), characterized by ultra-high dose rates (>40 Gy/s), has emerged as a novel irradiation modality capable of reducing normal tissue toxicity while preserving tumor control. This PhD project compares the radiobiological effects of FLASH-RT and CONV-RT using alternative in vivo models of pancreatic carcinoma, a malignancy associated with poor prognosis and limited therapeutic options. Chorioallantoic membrane (CAM) models were employed to assess treatment efficacy and toxicity, through quantitative analyses of tumor response, embryo survival, and developmental outcomes. FLASH-RT resulted in a significant reduction of off-target toxicity, as indicated by improved embryonic growth parameters, while achieving tumor control comparable to CONV-RT, thereby demonstrating iso-efficacy between the two irradiation modalities. These results support the hypothesis that FLASH-RT enhances the therapeutic ratio, particularly in the context of anatomically complex and radioresistant tumors such as pancreatic carcinoma. Furthermore, this work establishes a robust embryonic in vivo platform for the systematic evaluation of emerging radiotherapy strategies. Although further investigations are required to optimize dosimetric parameters and assess long-term biological effects, the present findings underscore the potential of FLASH-RT in redefining radiotherapy standards for challenging malignancies.