S2506
Radiobiology - Biology of novel irradiation techniques
ESTRO 2026
four-fraction irradiations (Fig. 1E), and with preliminary results of 1.12 (1.05-1.17) after eight fractions (Fig. 1F). Data collection on the eight-fraction treatments is ongoing.
Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 4 German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Purpose/Objective: Minibeam Radiation Therapy (MBRT) is an emerging preclinical radiotherapy modality that delivers arrays of spatially fractionated, millimeter-scale X-ray beams. This configuration generates alternating regions of high (peak) and low (valley) dose, enabling exceptional normal tissue sparing while maintaining tumor control comparable to conventional broad beam (BB) irradiation. Despite its promising therapeutic profile, the acute neurobehavioral consequences of MBRT remain insufficiently characterized. This study aimed to evaluate early and subacute behavioral changes following whole-brain MBRT in mice and compare them with effects induced by conventional BB exposure. Material/Methods: Adult C57BL/6 mice were irradiated at the FRM II facility (Garching, Germany) using the Line-Focus X-ray Tube (LFxT). MBRT was delivered as 260 μ m-wide planar beams spaced 1119 μ m apart, achieving a peak-to-valley dose ratio of 10 and an equivalent uniform dose (EUD) of 15 Gy. A comparison group received the same EUD via uniform BB irradiation. Behavioral testing was conducted at 7, 30, 60, and 90 days post-treatment and included the open field test (locomotion and anxiety-like behavior), Y-maze (spatial working memory and exploration), and acoustic startle response (sensorimotor gating). Results: Seven days after irradiation, MBRT-treated mice showed fewer center entries and altered center time distribution in the open field test (p ≤ 0.01), consistent with increased anxiety-like behavior. MBRT-exposed animals also demonstrated prolonged exit latency from the Y-maze start arm. Across the 90-day assessment period, MBRT mice developed mild but sustained hyperactivity (p ≤ 0.01), characterized by increased locomotor activity and reduced resting time. The early anxiety-like phenotype progressively resolved, and no significant deficits were found in spatial memory or sensorimotor gating. Conclusion: Whole-brain MBRT elicited transient anxiety-like behavior and mild long-term hyperactivity but did not produce major cognitive or sensorimotor impairments. Despite the high peak doses inherent to MBRT, overall neurobehavioral toxicity remained limited compared with conventional BB irradiation. These results reinforce MBRT’s favorable normal tissue tolerance and support its translation to clinical settings. Notably, future clinical applications are
Conclusion: The hypofractionated FLASH treatment retained the fibrotic sparing effect with a similar FLASH sparing for one fraction and four fractions, and preliminary data suggest a similar sparing for eight fractions. The maintained fibrotic sparing across fractionation schedules (Fig. 1D-F) were in stark contrast to the acute skin response of Kristensen et al. (2025) (Fig. 1A- C). Thus, it seems the fractionation-FLASH interaction differs between the acute skin response and the fibrotic response. In conclusion, fractionation and FLASH tissue-sparing interplay seem highly tissue-type
dependent. References:
Kristensen, L., Rohrer, S., Johansen, J. G., Hoffmann, L., Præstegaard, L. H., Hansen, A. H., Poulsen, P. R., & Sørensen, B. S. (2025). Fractionation increasingly reduces FLASH sparing for acute murine skin damage. Radiotherapy and Oncology, 213, 111209. https://doi.org/10.1016/J.RADONC.2025.111209 Keywords: FLASH, fractionation, fibrosis
Poster Discussion 1534
Minibeam radiation therapy (MBRT) induces mild hyperactivity with limited acute neurotoxicity in mice Thomas E Schmid 1,2 , Jessica Stolz 1 , Christian Petrich 1 , Johanna Winter 1 , Susanne Raulefs 1 , Paulina Hromekova 1 , Sabine Hölter 3,4 , Lillian Garrett 3,4 , Jan Einicke 3,4 , Bettina Sperling 3,4 , Stefan Bartzsch 1 , Stephanie E Combs 1,2 1 Department of Radiooncology, TUM University Hospital, TUM School of Medicine and Health, Muenchen, Germany. 2 Institute of Radiation Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 3 Institute of Developmental Genetics,
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