Multidisciplinary Approaches to The FLASH Radiotherapy

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Background

Radiotherapy (RT) is a cornerstone of cancer treatment, being routinely used for approximately half of cancer patients in high-income countries. Despite the extensive use of RT for over 60 years, its toxicity on normal tissues often limits the treatment of radioresistant tumors and is responsible for significant decrease in patient’s quality of life. However, it was recently established that ultra-high dose rate (UHDR) irradiation induces significantly less normal tissues toxicities, while keeping similar antitumor effect compared to conventional dose rate irradiation. This so called “FLASH Effect" was demonstrated in vivo on different animal models and different organs by delivering the total amount of radiation dose in a very short time ( usually <200 ms), with average dose rates above 40 Gy/s and with different particles including electrons, protons and photons.

While these promising results indicate bright prospects, the clinical translation is currently in the experimental phase, mainly due to two challenges. On one side, several technological issues must be addressed: the design of new devices capable of reproducibly delivering appropriately beams with fluences orders of magnitude higher than those used for conventional radiotherapy, and with an accurate real time beam monitoring system; the need of establishing an entirely new dosimetric protocol, since the "active" dosimeters used for conventional beams do not respond linearly at the UHDR regimes used in the FLASH-RT. The second challenge lies on the biology and is related to the absence of underlying biological mechanism explaining the differential radiobiological effect in cancer vs normal tissues exposed to FLASH-RT. Several hypotheses are currently considered, involving all the cascade of processes from the early radiation chemistry events, to the classical radiation-induced molecular and cellular mechanisms and tissue recovery processes. Nevertheless, no compelling evidence can yet confirm or refute these multiple hypotheses.

It is now obvious that the full clinical exploitation and optimization of FLASH-RT requires a multidisciplinary approach to best solve these multiple challenges. This involves multiple research topics: from the technological aspects of the beam production and characterization, to the final effects on cell and tissues, through the dose distribution and molecular-subcellular dynamics.

With this intent, we welcome in this Research Topic contributions aimed at investigating all the unclear aspects of this effects and addressed the related challenges, within a broad multi-disciplinary range. Accepted contributions might be related (but not limited to):

• Beam production and acceleration
• Real time beam monitoring technology and irradiation systems
• Dosimetry aspects and technology: new approaches or adaptation
• Physical characteristics of different types of radiations and beam time structure with respect to FLASH effect observation
• Biochemical and molecular biology studies and models of the sub-cellular effects of UHDR radiations
• Quantitative in vitro/in vivo analyses and design of new models to study the FLASH effect
• Clinical perspectives and first clinical trials of FLASH Radiotherapy
• Multi-scale modeling and simulations aimed at clarifying the molecular aspects of the FLASH effect

We accept a range of article types including Original Research and Review.

Keywords: Radiotherapy, Ultra-High-Dose-Rate radiations, dosimetry, radiobiology, multi-scale simulations, Medical accelerators, Molecular dynamics, Monte Carlo simulations, Kinetic models

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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