Dear Colleagues,

Without doubt, radiotherapy has seen noteworthy developments over the last few decades. Yet, therapies with significant impact on tumour control or sparing of normal tissues are still in their pre-clinical stages or waiting for clinical validation. Similar to the transition from standard (2Gy/fraction) to altered fractionation schedules, radiotherapy delivery underwent important evolutions from conventional to non-conventional administration.

FLASH radiotherapy is a novel, non-conventional irradiation technique that delivers ultra-high dose rates to the target, with excellent normal tissue sparing. While the mechanisms behind the enhancement of the therapeutic window owing to FLASH are not fully elucidated, there is considerable in vivo evidence that highlights the advantages of ultra-high dose rates compared to traditional radiotherapy.

High-dose spatially fractionated radiation, also known as GRID therapy, has been clinically evaluated over the last few decades using various grid designs to allow for a non-uniform dose delivery. With a similar concept, a more recently developed non-conventional irradiation technique employing minibeams via an array of closely spaced beams is appraised. This form of beam setting is thought to influence cell signalling via abscopal effects, leading to a difference in response between malignant and healthy cells.

Delivery of non-conventional radiotherapy was trialled with photons, electrons and proton beams alike. While showing real potential to widen the therapeutic window, these techniques require better understanding of the radiobiological and physico-chemical properties for further optimisation.

The aim of this Special Issue is to encompass both review articles and original research on the molecular and radiobiological aspects behind the success of non-conventional radiation delivery, including radiobiological modelling and laboratory research.

Articles focusing on the biological aspects behind non-conventional radiotherapy as well as studies within the field of experimental medicine demonstrating potential for translational research are encouraged.

Prof. Dr. Loredana Marcu
Guest Editor

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• non-conventional radiotherapy
• FLASH effect
• ultra-high dose rate
• minibeam
• GRID radiotherapy
• spatially fractionated irradiation
• normal tissue sparing