ImportanceTo our knowledge, there have been no clinical trials of ultra-high-dose-rate radiotherapy delivered at more than 40 Gy/sec, known as FLASH therapy, nor first-in-human use of proton FLASH.ObjectivesTo assess the clinical workflow feasibility and treatment-related toxic effects of FLASH and pain relief at the treatment sites.Design, Setting, and ParticipantsIn the FAST-01 nonrandomized trial, participants treated at Cincinnati Children’s/UC Health Proton Therapy Center underwent palliative FLASH radiotherapy to extremity bone metastases. Patients 18 years and older with 1 to 3 painful extremity bone metastases and life expectancies of 2 months or more were eligible. Patients were excluded if they had foot, hand, and wrist metastases; metastases locally treated in the 2 weeks prior; metal implants in the treatment field; known enhanced tissue radiosensitivity; and implanted devices at risk of malfunction with radiotherapy. One of 11 patients who consented was excluded based on eligibility. The end points were evaluated at 3 months posttreatment, and patients were followed up through death or loss to follow-up for toxic effects and pain assessments. Of the 10 included patients, 2 died after the 2-month follow-up but before the 3-month follow-up; 8 participants completed the 3-month evaluation. Data were collected from November 3, 2020, to January 28, 2022, and analyzed from January 28, 2022, to September 1, 2022.InterventionsBone metastases were treated on a FLASH-enabled (≥40 Gy/sec) proton radiotherapy system using a single-transmission proton beam. This is consistent with standard of care using the same prescription (8 Gy in a single fraction) but on a conventional-dose-rate (approximately 0.03 Gy/sec) photon radiotherapy system.Main Outcome and MeasuresMain outcomes included patient time on the treatment couch, device-related treatment delays, adverse events related to FLASH, patient-reported pain scores, and analgesic use.ResultsA total of 10 patients (age range, 27-81 years [median age, 63 years]; 5 [50%] male) underwent FLASH radiotherapy at 12 metastatic sites. There were no FLASH-related technical issues or delays. The average (range) time on the treatment couch was 18.9 (11-33) minutes per patient and 15.8 (11-22) minutes per treatment site. Median (range) follow-up was 4.8 (2.3-13.0) months. Adverse events were mild and consistent with conventional radiotherapy. Transient pain flares occurred in 4 of the 12 treated sites (33%). In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain).Conclusions and RelevanceIn this nonrandomized trial, clinical workflow metrics, treatment efficacy, and safety data demonstrated that ultra-high-dose-rate proton FLASH radiotherapy was clinically feasible. The treatment efficacy and the profile of adverse events were comparable with those of standard-of-care radiotherapy. These findings support the further exploration of FLASH radiotherapy in patients with cancer.Trial RegistrationClinicalTrials.gov Identifier: NCT04592887

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We have further developed a system for generating megavoltage CT images immediately prior to the administration of external beam radiotherapy. The detector is based on the scanner of Simpson (Simpson et al 1982)--the major differences being a significant reduction in dose required for image formation, faster image formation and greater convenience of use in the clinical setting. Attention has been paid to the problem of ring artefacts in the images. Specifically, a Fourier-space filter has been applied to the sinogram data. After suitable detector calibration, it has been shown that the device operates close to its theoretical specification of 3 mm spatial resolution and a few percent contrast resolution. Ring artefacts continue to be a major source of image degradation. A number of clinical images have been presented. The next stage of this work is to use the system to make clinical measurements of patient set-up inaccuracies building on our work making such measurements from digital portal images (Evans et al 1992).

Thin films of p-type ZnO:N have been obtained by thermally oxidizing zinc oxynitride films prepared by plasma enhanced chemical vapour deposition (PECVD). The p-type ZnO:N thin film with a hole concentration of 2.7 × 10 16 cm −3 was obtained after an annealing process was conducted at 600 • C. A conductivity transition from n-type to p-type was observed, which was systematically researched via structural and compositional analyses. In terms of these analyses, it helped to better understand the properties and behaviour of nitrogen in ZnO. First, nitrogen was incorporated into ZnO films during the growth process to occupy oxygen positions, and also partly compensated some donors induced from non-stoichiometric (ZnO 1-x ) composition. Second, the amount of activated nitrogen gradually increased in an oxidizing atmosphere and exceeded those donor states to realize an effective compensation, yielding p-type conductivity during the course of thermal oxidation.