Intra-operative electron radiation therapy: an update of the evidence collected in 40 years to search for models for electron-FLASH studies

Introduction: The clinical practice and outcome results of intraoperative electron radiation therapy (IOeRT) in cancer patients have been extensively reported over 4 decades. Electron beams can be delivered in the promising FLASH dose rate. Methods and Materials: Several cancer models were approached by two alternative radiobiological strategies to optimize local cancer control: boost versus exclusive IOeRT. Clinical outcomes are revisited via a bibliometric search performed for the elaboration of ESTRO/ACROP IORT guidelines. Results: In the period 1982 to 2020, a total of 19,148 patients were registered in 116 publications concerning soft tissue sarcomas (9% of patients), unresected and borderline-resected pancreatic cancer (22%), locally recurrent and locally advanced rectal cancer (22%), and breast cancer (45%). Clinical outcomes following IOeRT doses in the range of 10 to 25 Gy (with or without external beam fractionated radiation therapy) show a wide range of local control from 40 to 100% depending upon cancer site, histology, stage, and treatment intensity. Constraints for normal tissue tolerance are important to maintain tumor control combined with acceptable levels of side effects. Conclusions: IOeRT represents an evidence-based approach for several tumor types. A specific risk analysis for local recurrences supports the identification of cancer models that are candidates for FLASH studies.This research has been funded in part by grants from: Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, ERAPERMED PerPlanRT, AC20/00103, AC20/00102, 2020-110-1). Ministry of Science, Innovation and Education PID 2019-104558RB-100, Grant PID2019-110369RB-I00 (RADHOR), funded by MCIN/AEI/10.13039/50110001103