FLASH radiotherapy with photon beams

Abstract

Ultra‐high‐dose rate “FLASH” radiotherapy (FLASH‐RT) has been shown to drastically reduce normal tissue toxicities while being as efficacious as conventional dose rate radiotherapy to treat tumors. A large number of preclinical studies describing this so‐called FLASH effect have led to the clinical translation of FLASH‐RT using ultra‐high‐dose rate electron and proton beams. Although the vast majority of radiation therapy treatments are delivered using X‐rays, few preclinical data using ultra‐high‐dose rate X‐ray irradiation have been published. This review focuses on different methods that can be used to generate ultra‐high‐dose rate X‐rays and their beam characteristics along with their effect on the biological tissues and the perspectives for the development of FLASH‐RT with X‐rays.

A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy

“…1 Although the underlying radiobiological mechanism of the FLASH effect remains elusive and is under active investigation, 21,22 these promising preclinical results have inspired translational efforts to realize a wide range of delivery platforms with UHDR capabilities. [23][24][25][26][27][28][29][30] Although FLASH-RT delivered with electrons has produced the majority of preclinical results to date, 1,[5][6][7][8] electron FLASH-RT is limited in its eventual clinical translation to treat deep-seated targets with sufficient conformity due to the properties intrinsic to electron interactions. 4 FLASH-RT delivery using proton therapy has emerged as an attractive alternative because of its excellent dose conformity, its ability to treat deepseated targets, and the availability of existing treatment machines to deliver at UHDR.…”

A roadmap to clinical trials for FLASH

“…Other papers in this issue highlight the variety of radiotherapy types used to deliver UHDR to date: electrons, photons, protons, and light ions. [47][48][49] Multimodality clinical trials will require careful consideration of machine capabilities, differences in dose prescriptions, radiobiology, etc. Early clinical trials would optimally be powered to see if different FLASH modalities caused different outcomes using patients as their own controls if possible.…”

“…Other papers in this issue highlight the variety of radiotherapy types used to deliver UHDR to date: electrons, photons, protons, and light ions 47‐49 . Multi‐modality clinical trials will require careful consideration of machine capabilities, differences in dose prescriptions, radiobiology, etc.…”

A high‐resolution dose calculation engine for X‐ray microbeams radiation therapy

“…The outcome of radiation therapy in terms of efficacy and toxicity relies on a compromise made between maximizing the deposited radiation dose in the tumoral area and minimizing the damage to healthy tissues by keeping the radiation dose delivered to these organs as low as possible 1 . Microbeam radiation therapy (MRT) is a disruptive radiotherapy approach aiming at widening the therapeutic window by combining the spatial fractionation of synchrotron generated X‐rays into an array of intense parallel microbeams (25–50‐μm wide beams replicated with a pitch of 200–400 μm) with an irradiation performed at high dose rate to benefit from the improved healthy tissue tolerance due to the FLASH effect 2–4 . MRT pushes the concept of dose–volume effect to its theoretical limits with high doses delivered in the microbeam paths (peak doses), whereas low‐dose areas are found in‐between these tracks (valley doses).…”

“…1 Microbeam radiation therapy (MRT) is a disruptive radiotherapy approach aiming at widening the therapeutic window by combining the spatial fractionation of synchrotron generated X-rays into an array of intense parallel microbeams (25-50-µm wide beams replicated with a pitch of 200-400 µm) with an irradiation performed at high dose rate to benefit from the improved healthy tissue tolerance due to the FLASH effect. [2][3][4] MRT pushes the concept of dose-volume effect to its theoretical limits with high doses delivered in the microbeam paths (peak doses), whereas lowdose areas are found in-between these tracks (valley doses). Several preclinical studies have demonstrated the potential of MRT for improving tumor control with reduced side effects.…”