ESTRO 2021 Abstract Book

S555

ESTRO 2021

radiation dose and the quantification of its distribution. Mathematical models in radiobiology provide a framework to enable us to plan a patient treatment for a specific outcome. The exponential relation of dose with biological response, originally described by the linear quadratic (LQ) equation of Lea and Catcheside dating back to the 1940s, has seen many inclusions in response to experimental refinements, advances in treatment methods or clinical observations. However, there is little to discriminate between the predictions of a range of empirical models when compared to observed data, motivating the trend towards developing mechanistic models to describe radiation response. Although the physics of radiation dose absorption is well understood, the subsequent mechanisms of biochemical response, release of metabolites and their decay leading to a radiation response is not understood in its entirety and is an area of some considerable current interest. Current and emerging treatment techniques and protocols, such as SBRT, Flash treatments, spot scanning and pulsed treatments, inherently introduce temporal or spatial modulation of dose, stimulating a level of biological complexity that traditional radiobiology was never designed to predict. Radiation induced bystander effects, which have been reported to be responsible for 60% to 80% of all cell death in radiotherapy are still not specifically targeted in treatment prescriptions. Although current technology can now deliver elegant treatments, such as choreographed proton beams that can deliver a radiation dose modulated in time and space, we are still focussed on physical targets. The potential promised by biological targeting is compelling. Clinically, there is now extensive experience to show that identical treatment of similar tumours, even with a standard technique, will result in a broad range of patient response (~25%). This is commonly attributed to differences in individual patient DNA mutations and tumour microenvironment but may also reflect our inability to drive the biology. Furthermore, few of our patients are treated with radiation therapy alone and incorporation of other treatments, especially new immunotherapy vectors, is needed for a comprehensive patient treatment plan. Current clinical variability in radiobiological response means that, despite careful physical targeting, many patients are either over or under treated. We have the engineering capacity and physical precision to deliver the radiation dose, however, to optimise the patient treatment response to the next level, a better understanding of the biochemical and biomolecular response leading to the overall patient response is needed. Physicists play an important role in synthesizing the experimental and clinical data, from current and emerging treatments, but a multidisciplinary team is needed to take the next major step to develop predictive radiobiological models for comprehensive treatment planning aimed at personalized biological response. Acknowledgements Funding from: Catalyst Seed Funding Tour de Cure Foundation The Prostate Cancer Foundation of Australia The Ian Potter Foundation The University of Sydney ECR/MCR Seeding Grant NHMRC Ideas Grant Australian Commonwealth Government Grant SP-0719 FLASH radiotherapy R. Moeckli 1 1 Lausanne University Hospital and Lausanne University, Institute of Radiation physics, Lausanne, Switzerland Abstract Text FLASH radiotherapy (FLASH RT) has gained attention in radiation therapy research, because it has been observed that when the dose is delivered at ultra-high dose rate (UHDR), a biological effect called FLASH effect appears. It is sparing normal tissues whereas the tumor control remains the same compared to conventional irradiations. The FLASH effect was observed with typical irradiations of less than 100ms and a mean dose rate of at least 100Gy/s, in different animal species (fish eggs, mice, cats and pigs) and a first patient was treated in 2019. Most of the experiments were performed with UHDR electron beams, but also with photons and protons. The redundant observations of FLASH effect on animals, makes it relevant for clinical transfer and clinical protocols have been recently started. However, there are important remaining questions that have to be answered. The biological cause of FLASH effect is not yet fully understood and the physical parameters of the beams that trigger FLASH effect are not fully defined. The metrological traceability of the dose at UHDR is not yet established and most of the time redundant dosimetry is used to characterize the delivered dose. The type of beams to be used, particularly related to the field size, is still a question to be debated, and which one between very high energy electron (VHEE), protons or photons beams are best suited for the treatment of deep-seated tumors remains an open question. Finally, a safe and reliable use of FLASH RT is mandatory for the clinical transfer and the short duration of the irradiations need new control systems that still have to be developed. FLASH RT is a highly promising way for the treatment of cancer in radiation therapy, but important questions remain to be solved before a large dissemination of that treatment technique will become possible in clinical practice.

SP-0720 Microbeam radiotherapy M. Krisch France

Abstract not received

Symposium: The impact of immoblisation/positioning in advanced radiotherapy