FLASHRadiotherapy Enhances the Therapeutic Ratioin an Embryonic In Vivo Model of Pancreatic Carcinoma

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Radiotherapy (RT)is a commonly employed treatment in oncologicalsetting. Unfortunately, the therapeutic dose required for tumor controloften induces significant side effects in normal tissues, leadingto suboptimal outcomes and reduced patient quality of life. FLASHradiotherapy (FLASH-RT) is distinguished by its exceptionally highdose rates, surpassing 40 Gy/s. This advancement has emerged as apromising innovation in the field of cancer treatment. Indeed, FLASH-RTmay reduce normal tissue toxicity compared to conventional radiotherapy(CONV-RT) while maintaining tumor control. Here, FLASH-RT and CONV-RThave been compared in an alternative embryonic model of pancreaticcarcinoma, a cancer type with poor prognosis and limited therapeuticoptions. The chorioallantoic membrane models (CAMs) have been employedto assess the tumor control and the treatment toxicity by analyzingthe embryo survival. FLASH-RT exhibited significantly reduced off-targettoxicity on the embryos, as evidenced by the embryonic growth analysisand histopathological analysis. The tumor control outcomes were comparablebetween FLASH-RT and CONV-RT, confirming the iso-efficacy betweenthe two strategies. These findings confirm the paradigm-shifting potentialof FLASH-RT to enhance the therapeutic ratio, particularly in anatomicallycomplex and radioresistant tumors such as pancreatic carcinoma, warrantingfurther investigation in clinical settings. Additionally, a solidembryonic in vivo model has been introduced for comprehensiveinvestigations on emerging radio-treatment approaches. While furtherinvestigations are necessary to optimize dose delivery and evaluatelong-term outcomes, this research underscores the transformative promiseof FLASH-RT in redefining radiotherapy standards for challenging malignancies.