Global clinical landscape and multidisciplinary translational frontiers of FLASH radiotherapy: a systematic review...

Ultra-high dose rate FLASH radiotherapy (FLASH-RT) holds the potential to revolutionize oncology by dramatically sparing normal tissue while maintaining tumor control. To capture both physical breakthroughs and biomedical translation, this study provides a comprehensive bibliometric mapping to evaluate the global research landscape and translational frontiers of FLASH-RT.

To ensure maximum comprehensiveness, a systematic dual-database retrieval was conducted using the Web of Science Core Collection (WoSCC) and PubMed for articles published between January 1, 2014, and December 31, 2025. Following software-assisted deduplication using bibliometrix and independent, researcher-guided manual screening to exclude non-relevant document types, analytical protocols utilizing the R package bibliometrix, VOSviewer, and CiteSpace were applied to visualize publication trends, co-authorship networks, and keyword bursts.

A final analytical cohort of 807 high-quality articles was identified, revealing a rapidly accelerating, non-linear growth pattern relative to the 2014 baseline, with a marked surge after 2021, corresponding to the onset of prospective human FLASH-RT trials. The fitted annual-output trend followed a quadratic polynomial model with R² = 0.9458. The United States (30.4%) and China (18.7%) led quantitatively, while Switzerland drove deep multi-institutional innovation. We identified a definitive interdisciplinary paradigm shift: early investigations focused on fundamental physics and X-ray dosimetry, whereas contemporary research has rapidly pivoted toward proton FLASH therapy, oxygen depletion kinetics, and phase-1 clinical workflows. Furthermore, keyword burst detection highlighted "ion recombination" and "delivery methods" as the most critical ongoing technical challenges.

By integrating extensive data from both WoSCC and PubMed, this study documents the safety-led maturation of FLASH-RT from an experimental physics curiosity to a viable clinical precision tool. The evolving synergy between dose-rate optimization and clinical oncology emphasizes that solving real-time dosimetric challenges remains the essential frontier for achieving widespread clinical adoption and widening the therapeutic window.