FLASH Radiotherapy Enhances the Therapeutic Ratio in an Embryonic In Vivo Model of Pancreatic Carcinoma

Radiotherapy (RT) is a commonly employed treatment in oncological setting. Unfortunately, the therapeutic dose required for tumor control often induces significant side effects in normal tissues, leading to suboptimal outcomes and reduced patient quality of life. FLASH radiotherapy (FLASH-RT) is distinguished by its exceptionally high dose rates, surpassing 40 Gy/s. This advancement has emerged as a promising innovation in the field of cancer treatment. Indeed, FLASH-RT may reduce normal tissue toxicity compared to conventional radiotherapy (CONV-RT) while maintaining tumor control. Here, FLASH-RT and CONV-RT have been compared in an alternative embryonic model of pancreatic carcinoma, a cancer type with poor prognosis and limited therapeutic options. The chorioallantoic membrane models (CAMs) have been employed to assess the tumor control and the treatment toxicity by analyzing the embryo survival. FLASH-RT exhibited significantly reduced off-target toxicity on the embryos, as evidenced by the embryonic growth analysis and histopathological analysis. The tumor control outcomes were comparable between FLASH-RT and CONV-RT, confirming the iso-efficacy between the two strategies. These findings confirm the paradigm-shifting potential of FLASH-RT to enhance the therapeutic ratio, particularly in anatomically complex and radioresistant tumors such as pancreatic carcinoma, warranting further investigation in clinical settings. Additionally, a solid embryonic <i>in vivo</i> model has been introduced for comprehensive investigations on emerging radio-treatment approaches. While further investigations are necessary to optimize dose delivery and evaluate long-term outcomes, this research underscores the transformative promise of FLASH-RT in redefining radiotherapy standards for challenging malignancies.