The Therapeutic Potential of FLASH-RT for Pancreatic Cancer

SIMPLE SUMMARY: Ultra-high dose rate radiation, widely nicknamed FLASH-RT, kills tumors without significantly damaging nearby normal tissues. This selective sparing of normal tissue by FLASH-RT tissue is called the FLASH effect. This review explores some of the proposed mechanisms of the FLASH effect and the current data that might support its use in pancreatic cancer. Since radiation for pancreatic cancer treatment is limited by GI toxicity issues and is a disease with one of the lowest five-year survival rates, FLASH-RT could have a large impact in the treatment of this disease with further study. ABSTRACT: Recent preclinical evidence has shown that ionizing radiation given at an ultra-high dose rate (UHDR), also known as FLASH radiation therapy (FLASH-RT), can selectively reduce radiation injury to normal tissue while remaining isoeffective to conventional radiation therapy (CONV-RT) with respect to tumor killing. Unresectable pancreatic cancer is challenging to control without ablative doses of radiation, but this is difficult to achieve without significant gastrointestinal toxicity. In this review article, we explore the propsed mechanisms of FLASH-RT and its tissue-sparing effect, as well as its relevance and suitability for the treatment of pancreatic cancer. We also briefly discuss the challenges with regard to dosimetry, dose rate, and fractionation for using FLASH-RT to treat this disease.