ESTRO 2025 Congress Report
By the ESTRO FLASH focus group
At this year’s ESTRO congress, FLASH radiotherapy was one of the most eagerly anticipated and extensively debated topics, engaging experts across disciplines. The emphasis on FLASH reflected the community’s proactive stance toward clinical integration.
The FLASH journey started with a focus on the fundamentals. In an extensive teaching lecture, Dr Anna Subiel (UK) and Dr Francesco Romano (Italy) detailed the current landscape of dosimetry and instrumentation for ultra-high-dose-rate (UHDR) radiotherapy. They noted that although the current primary standards and calorimeters show promise, no unified dosimetric framework has been developed. Dr Subiel emphasised the necessity of traceability and the adaptation of protocols, such as TRS-398, for UHDR delivery. Dr Romano presented emerging detector technologies, including solid-state detectors and portable calorimeters, which could facilitate future clinical workflows. Together, they laid the groundwork regarding the technical precision that is essential for the safe clinical implementation of FLASH radiotherapy.
In the session titled “Future of proton therapy: which innovation will have the biggest impact?”, Professor Brita Singers Sørensen (Denmark) showcased compelling preclinical data on proton FLASH that illustrated its consistent tissue-sparing effects and the critical role of beam delivery dynamics, particularly the influence of beam pauses. During the session “Back to the future: electron treatments today and tomorrow”, Dr Jake Pensavalle and Dr Gaia Franciosini (both from Italy) delved into the potential of using very-high-energy electrons (VHEE) to apply FLASH radiotherapy to deep-seated tumours. Their work on accelerator design and treatment planning provided insights into the future of FLASH-capable systems.
A multidisciplinary panel that featured Dr Marta Capala (The Netherlands), Professor Martin Pruschy (Switzerland), and Dr Elise Konradsson (USA) and was moderated by Professor Pierre Montay-Gruel (Belgium) addressed a critical issue: how FLASH radiotherapy can be safely and effectively transitioned from bench to bedside. While acknowledging that the biological mechanisms of FLASH are not yet fully understood, the panel stressed the importance of mitigating risks in early-phase trials by pinpointing factors that could influence biological responses. They advocated the use of innovative trial designs and the inclusion of veterinary patients (pets) with spontaneous tumours as these would be more realistic models for assessment of safety and efficacy than than preclinical animal models with induced tumours. The questions (some of which were provocative) from the participants highlighted some unresolved issues and unanswered questions, but the discussion made it clear that the community was ready to undertake clinical trials using FLASH. It has been stated several times that only clinical data (from carefully planned and executed trials) can bring us closer to answering some of the burning questions regarding the FLASH effect.
The scientific programme was abundant with new data. In the proffered paper sessions, Prof Montay-Gruel presented transcriptomic data illustrating that FLASH radiotherapy triggered a complex immune response in triple-negative breast cancer while concurrently reducing inflammation in healthy lung tissue, and that macrophages were significantly involved. Dr Konradsson demonstrated that use of single-fraction, single-pulse FLASH significantly diminished acute skin toxicity in a mouse model. On the physics side, Dr Romano validated the use of a portable graphite calorimeter for UHDR beams. Several PhD students presented their work: Hayden Scott (USA) introduced an innovative remote quality assurance system that utilised semiconductor detectors; Marina Orts Sanz (Belgium) proposed a dual-gap ionisation chamber for real-time recombination correction; and Gavin Pikes (Australia) employed Monte Carlo simulations to investigate radical yield dynamics. Additionally, Dr Florian Amstutz (Switzerland) presented planning of focused VHEE treatment as a promising strategy for targeting deep tumours.
The mini-oral presentations provided a good view of the clinical horizon. Dr Rémy Kinj (Switzerland) presented early data on safety from a Phase I trial (LANCE) on melanoma skin metastases, which showed that there were no dose-limiting toxicities up to 28Gy in a single fraction. Dr Anouk Sesink (Switzerland) identified a 100Gy/s threshold for intestinal sparing in mice and illustrated how oxygenation and fractionation could reduce the FLASH effect. Dr Konradsson demonstrated that FLASH was safe and well-tolerated when administered using a standard-of-care hypofractionated regimen in a porcine skin model. Meanwhile, PhD student Filip Hörberger (Sweden) showed models of net-sparing effects that revealed benefits of the use of FLASH in breast and prostate cases, though not across all tumour sites.
Collectively, these contributions underscore a multidisciplinary endeavour to harness the full potential of FLASH radiotherapy. By the conclusion of ESTRO 2025, it was clear that what was once a niche area of experimental research has evolved into a central focus of innovation, discussion, and cautious optimism. Despite ongoing challenges, the advancements showcased at ESTRO 2025 outline a clear and coordinated trajectory toward clinical implementation.
Dr Elise Konradsson, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (ekkonradsson@mdanderson.org)
Member of the ESTRO FLASH focus group
Professor Pierre Montay-Gruel, Radiation Oncology Department, Iridium Netwerk, Wilrijk (Antwerp), Belgium; Antwerp Research in Radiation Oncology (AReRO), Centre for Oncological Research (CORE), University of Antwerp, Belgium (pierre.montaygruel@zas.be)
Core expert of the ESTRO FLASH focus group
Dr Marta Capala, Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, The Netherlands (m.capala@erasmusmc.nl)
Member of the ESTRO FLASH focus group