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What is FLASH radiotherapy?

Karl Butterworth radiotherapy Stephen McMahon

FLASH radiotherapy is an emerging technique in cancer treatment that delivers radiation at ultra high dose rates – typically above 40-50Gy/s – within milliseconds, compared to conventional rates of about 0.03Gy/s over several minutes. The central goal of radiotherapy has always been to maximise tumour control while minimising normal tissue toxicity. Traditional approaches rely on precise targeting and fractionation, but toxicity remains a limiting factor. FLASH radiotherapy offers a potential breakthrough by exploiting a phenomenon known as the ‘FLASH effect,’ where normal tissues exhibit significant sparing while tumour control remains unchanged.

First demonstrated in 2014 by Vozenin and colleagues in mouse models, FLASH radiotherapy nearly doubled the dose required to induce lung toxicity compared to conventional delivery, without compromising tumour response. This discovery has spurred extensive research, confirming FLASH sparing across multiple tissues and animal models. Although the exact mechanism remains unclear, hypotheses include transient oxygen depletion and other biochemical changes occurring within sub-second timescales.

Clinical translation is underway, with early trials such as the FAST-01 proton FLASH study showing feasibility and safety in treating bone metastases. However, challenges persist: current systems can only deliver FLASH for simple, single-field treatments, and fractionation or complex beam modulation reduces the effect. Moreover, no human trials have yet quantified the magnitude of FLASH sparing.

If preclinical benefits translate clinically, FLASH radiotherapy could revolutionise cancer treatment by reducing side effects and enabling higher therapeutic doses. Yet, technological and biological uncertainties demand cautious, evidence-driven implementation.

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