Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called "FLASH-RT" and irradiation delivered at a conventional dose rate called "Conv-RT." A clinical, phase I, single-dose escalation trial (25-41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%.C Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients.

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The LGK Icon was successfully commissioned for clinical use. The use of the EBT3 to characterize the treatment unit was demonstrated to be feasible. The CBCT imaging system operates well within the manufacturer's specifications and provides good geometrical accuracy.

BACKGROUND:Stereotactic radiosurgery has become a common treatment approach for small-to-medium size vestibular schwannomas.OBJECTIVE:To evaluate relationship between time (beam-on and treatment) and risk of hearing decline after stereotactic radiosurgery for vestibular schwannomas in patients with Gardner–Robertson (GR) baseline classes I and II.METHODS:This retrospective longitudinal single-center study included 213 patients with GR I and II treated between June 2010 and December 2019. Risk of passing from GR classes I and II (coded 0) to other classes III, IV, and V (coded 1) and the increase in pure tone average (continuous outcome) were evaluated using a mixed-effect regression model. Biologically effective dose (BED) was further assessed for an alpha/beta ratio of 2.47 (Gy2.47).RESULTS:Binary outcome analysis revealed sex, dose rate, integral dose, time [beam-on time odds ratio 1.03, P = .03, 95% CI 1.00-1.06; treatment time (P = .02) and BED (P = .001) as relevant. Fitted multivariable model included the sex, dose rate, and BED. Pure tone average analysis revealed age, integral dose received by tumor, isocenter number, time (beam-on time odds ratio 0.20, P = .001, 95% CI 0.083-0.33) and BED (P = .005) as relevant.CONCLUSION:Our analysis showed that risk of hearing decline was associated with male sex, higher radiation dose rate (cutoff 2.5 Gy/minute), higher integral dose received by the tumor, higher beam-on time ≥20 minutes, and lower BED. A BED between 55 and 61 was considered as optimal for hearing preservation.